World Journal of Nuclear Medicine

World Journal of Nuclear Medicine

Volume 4, Supplement 1, October 2005

Published by WFNMB

Online: www.wjnm.org

WORLDFEDERATION

OFNUCLEAR

MEDICINEAND

BIOLOGY

INTERNATIONAL CONFERENCE ONRADIOPHARMACEUTICAL THERAPY

(ICRT-2005)

11-14 October 2005Limassol, Cyprus

World Journal of Nuclear MedicineVolume 4, Supplement 1, October 2005

Editorial

Padhy AK S-1

S-12

S-66

Therapeutic Nuclear Medicine: It is time to act

WFNMB/WRPTC International Conference on Radiopharmaceutical Therapy

Scientific Programme S-3

Abstracts

Index of Authors

World J Nucl Med 2005; 4: S1 - S67

General Information

Target Group:

Contents:a.General:

b. Related to WFNMB:

c. Related to IAEA and other International organizations:

d. Research & Development:

e. Windows for the Industry

This will be a publication of the World Federation of Nuclear Medicine & Biology (WFNMB) with the support of the IAEA and will be published quarterly. The purposes of the journal are as follows:

To be an official publication of the World Federation of Nuclear Medicine & Biology (WFNMB) with the active collaboration and support of the IAEATo promote research in nuclear medicine globally and in the developing countries in particularTo promote good practice in nuclear medicine

All members of the WFNMBAll member states of IAEASpecialists belonging to various fields of nuclear medicine (Physicians, radiopharmacists, physicists, radioimmunoassayists, molecular biologists, etc.), technologists and nursesManufacturers of equipment and reagents relevant to nuclear medicineAtomic Energy Commissions, Governmental and administrative personnel relevant to nuclear medicine practice in the various countries

Reviews related to the good practice of nuclear medicine

NewsletterAnnouncementsReports of working groups, etc.Editorials on WFNMB Planning & Strategy etc.Abstracts of Congresses

NewsletterAnnouncementsReports of CRPs, RCMs, SeminarsAbstracts of International SeminarsPeriodic world status reportsRegional Windows EditorialsCochrane Reviews

CMEs on Clinical subjects as well as on Science & Technology pertaining to nuclear medicineOriginal articlesLetters to the editor

(coloured pages)

!

!

!

!

!

!

!

!

Display Commercial Advertising

Editorial Office

ISSN Number (print) 1450-1147

Production

Cover Design

Graphic Design

PrintersJagannath Printing Press, New Delhi, India

Electronic Edition

WebMaster

Copyright

It is hoped that the nuclear medicine industry (radiopharmaceuticals, nuclear instrumentation, computer & reagents etc.) will view the journal as an effective means of advertising to the nuclear medicine community. In order that the journal can be self-sustaining, we invite the industry to provide significant support and to assist in raising the profile of this important journal, the first to specifically target the world-wide nuclear medicine community. Besides regular full, half and quarter page advertisements, the journal will also publish special features like "windows for the industry". All advertising materials accepted are expected to conform to ethical, medical and business standards. Acceptance does not imply endorsement by the journal.

World Journal of Nuclear MedicineNuclear Medicine DepartmentKF Nuclear Diagnostics Filiou Zannetou 10CY-3021 LemesosTel.:+357 25878725Fax:+357 25871747e-mail: [email protected]

KF Nuclear Diagnostics Ltd.Filiou Zannetou 10CY-3021 LemesosCyprusTel.:+357 25878725Fax:+357 25871747e-mail: [email protected]

Mr. Anatoli Bourykine (IAEA)

Mr. Bankim Desai

ISSN Number (online) 1607-3312www.wjnm.org

Marios Pieri, Nicosia, Cyprus

© World Journal of Nuclear Medicine, 2005

World Journal of Nuclear Medicine

Editorial BoardEditor in Chief :Executive Editors :Senior Editor :Editor (IAEA) :Treasurer :Regional Editors :

Assistant Editors :

K.E. Britton

A.K. Padhy, H. Amaral, J.K. Chung

S. Frangos

M. Dondi

W. Choe

Africa: A. Ellmann, Asia: H. Sakahara, China & Fow East : M-Tian,Europe: A. Signore, N. America: C. Divgi,South and Central America: O. Estrella Anselmi, West Asia: M. Al-Zboun,

A.Soricelli, G. Hinterleitner, N. Watanabe

Members :Aas M (Norway)Abdel-Dayem H (USA)Abdul Khader MA (Malaysia)Adel Bakir M (Syria)Al-Nahhas A (UK)Alvarado N (Peru)Andreo P (Sweden)Barrenechea E (Philippines)Batista Cuellar JF (Cuba)Baum RP (Germany)Belohlavek O (Czech Republic)Bernal P (Colombia)Biersack H-J (Germany)Bouyoucef SE (Algeria)Buscombe J (UK)Chaiwatanarat T (Thailand)Chianelli M (Italy)Corstens FHM (The Netherlands)Duffy G (Ireland)Dziuk M (Poland)El-Desouki M (Saudi Arabia)El-Gazzar A-H (Kuwait)Fernandes O (Brazil)Fettich J (Slovenia)Fonseca Zamora CA (Costa Rica)Fraxedas R (Cuba)Garcia E (Mexico)Goldsmith SJ (USA)Gomo ZAR (Zimbawbe)Granowska (UK)He Zuo-Xiang (china)Henricksen JH (Denmark)Hesselwood S (UK)Hoeflin F (Switzerland)Horne T (Israel)Hussein K (Indonesia)Hatton B (UK)Jafri RA (Pakistan)Kabasakal L (Turkey)Karim MA (Bangladesh)Knapp FF (USA)Kouris K (Cyprus)Kropp J (Germany)Kumar V (Australia)Lass P (Poland)Lepej J (Slovakia)Lind P (Austria)Liu XJ (China)

M'Timet S (Tunisia)Magzoub MAA (Sudan)Malamitsi J (Greece)Mather S (UK)Maunda KKY (Tanzania)McEwan AJW (Canada)Meneghetti JC (Brazil)Moustafa H (Egypt)Mut F (Uruguay)Obaldo J (Philippines)Obradovic V (Serbia & Montenegro)Olarrechea M (Bolivia)Oliva JP (Cuba)Orellana P (Chile)Palazzi F (Venezuela)Pant GS (India)Petrovici R (Romania)Piepsz AM (Belgium)Piperkova E (Bulgaria)Prigent A (France)Roca I (Spain) Rodrigues Radischat M (Austria)Rutland M (New Zeland)Saghari M (Iran)Salvatore M (Italy)Samuel AM (India)Sasaki Y (Japan) Sixt R (Sweden)Soroa V (Argentina)Srivastava S (USA)Stabin M (USA)Stare J (Slovenia)Sundram FX (Singapore)Szilvasi I (Hungary)Taiffeur R (Canada)Thakur ML (USA)Tonami N (Japan)Turner HJ (Australia)Vassilakos PJ (Greece)Vera Ruiz H (IAEA)Viera R (Portugal)Vinjamuri S (UK)Virgolini I (Austria)Watawana L (Sri Lanka)Wenzel K von (Namibia)Yonekura Y (Japan)Zakko S (UAE) Zanzonico P (USA)Zhang H (China)

World Journal of Nuclear Medicine, Volume 4, Supplement 1, October 2005

International Conference on Radiopharmaceutical Therapy(ICRT-2005)

11-14 October 2005

Venue:

Organised by:

In Collaboration with

Limassol, Cyprus

St Raphael ResortLimassol, Cyprus

World Radiopharmaceutical Therapy CouncilA subsidiary body of

World Federation of Nuclear Medicine & Biology (WFNMB)

The Cyprus Society of Nuclear Medicine

December heralds the season of greetings and wishes. It is our great pleasure to invite you to the Annual conference of Society of Nuclear Medicine(India) of the year 2005 which is scheduled for coming December 08 to 11th in Calicut, Kerala. The theme of the conference "Scroll in to the era of Fusion Imaging" has been chosen to reflect the rapid changes and the future opportunities of Nuclear Medicine in India with a global perspective.

Being one of the most beautiful places on earth, Kerala promises a wonderful experience to your expectation.

Dr. G. RijjuSecretary General SNMI 2005Department of Nuclear MedicineMalabar Institute of Medical Sciences (MIMS)Govindapuram POMini Bypass RoadCalicut - 673 016 Kerala. INDIA.Tel : 0495-2744000 Fax : +91 495 2741329 Mobile : 9387521555E-mail : [email protected],

[email protected] :http://www.malabarinstitute.com http://www.iasnm.org

For More Details Contact :



A.K. PadhyExecutive Editor, WJNM & Scientific Secretary-ICRT 2005

It is my great pleasure inviting you to the First International Conference on Radiopharmaceutical Therapy (ICRT-2005) being organised by the World Radiopharmaceutical Therapy Council (WRPTC). World Radiopharmaceutical Therapy Council is a subsidiary body of the World Federation of Nuclear Medicine and Biology (WFNM&B) with stake holders from all fields of nuclear medicine, several allied clinical specialties as well as from the industry including nuclear medicine physicians, radio-chemists, physicists, oncologists, rheumatologists, endocrinologists and scientists, who share research commitments to, and clinical practice in, therapeutic nuclear medicine. The major objective of the WRPTC includes se t t ing s tandards for provis ion of radiopharmaceutical therapy, particularly in the development of uniform protocols for application worldwide. Radionuclides are being used extensively to provide palliative and curative treatment in a number of benign and malignant diseases. The potential of radionuclides for treating diseases has been recognized and put to use for the past several decades. It has been possible to exploit the physiology unique to an organ or a disease process to deliver the radionuclides selectively to the sites of abnormality. Radioiodine treatment of thyroid diseases (Thyroid cancer, Hyperthyroidism etc.), I-131 MIBG therapy of neuro-endocrine tumours, radio-immunotherapy of B-cell lymphoma, palliative treatment of metastatic bone pain using bone seeking radiopharmaceuticals, radiosynovectomy and intravascular radionuclide therapy using liquid sources of radioactivity to prevent restenosis in patients following percutaneous Tran-luminal coronary angioplasty (PTCA) have all been established in therapeutic nuclear medicine. The use of Rhenium 188 labelled compounds is rapidly increasing in the treatment of a number of benign and malignant disorders, including liver cancer (Re-188 Lipiodol), especially in developing countries. To-day radiopharmaceutical therapy is one of the fastest growing branches of nuclear medicine. However, its practice in developing countries is only beginning to gain ground after years of trailing behind its use in the developed world. The establishment and consolidation of radiopharmaceutical therapy has come about as a result of a gradual change in the realization of its importance, cost-effectiveness and practicality. Availability of new generator produced, beta emitting radiopharmaceuticals like Re-188 for use in hospital radiopharmacy facilities has also

enhanced the scope and practice of radionuclide therapy using radiopharmaceuticals prepared on site within the nuclear medicine-radiopharmacy dispensaries. The objectives of this conference are to evaluate the current status of radiopharmaceutical therapy in the world in general and in the developing countries in particular, to exchange information on the current advances in the field between scientists from developed and developing countries; to interact with user groups (clinicians, oncologists, surgeons, radiopharmacists, medical physicists, etc.) and to bring them the most important information in the field, and to define future directions.The Symposium will cover topics and issues on all aspects of radiopharmaceutical therapy through a number of plenary lectures, papers, panel discussions and interactive audiovisual sessions. The topics to be addressed at the symposium include reviews in therapeutic radiopharmaceuticals, development of new radiopharmaceuticals, clinical overviews of the current trends in radionuclide therapy, clinical applications (radionuclide therapy of primary cancers, treatment of metastatic disease, pain palliation and treatment of benign diseases like rheumatoid arthritis, haemophilic haemarthrosis, hyperthyroidism etc.), prognostication in cancer therapy, dosimetry, patient monitoring , molecular methods in radiopharmaceutical therapy, treatment planning, use of new instruments (PET/CT, dedicated cameras, hand held cameras, etc.) in radiopharmaceutical therapy planning, drug resistance, radio-immuno detection and therapy, infrastructure development , training and education. Through organization of this conference we expect to accomplish the following: 1. To carry out an evaluation of the current status of radiopharmaceutical therapy globally, 2. To help in the transfer of important information on the current trends in radiopharmaceutical therapy from developed to developing countries, 3. To publish a technical document based on the proceedings of the Symposium, 4. To promote radiopharmaceutical therapy globally in general, and in developing countries in particular and 5. To formulate a strategy document for promoting radiopharmaceutical therapy around the world. It is heartening to see overwhelming response to our efforts in the organization of this conference. We have a pre-conference registration of 175 participants and received 122 abstracts for presentation. This is considered remarkable for a conference of this type. It is also remarkable that 70% of the abstracts received are from the developing countries, which in itself is an indication that radionuclide therapy is slowly but steadily being accepted as a treatment modality in many parts of the developing world.It is expected that International organizations like

Editorial

Therapeutic Nuclear Medicine: It is time to act

S-1


WFNMB, IAEA, WRPTC, SNM, EANM, ALASBMN, A O F N M B a n d A R C C N M a s w e l l a s t h e radiopharmaceutical industry would rise to the occasion and take full advantage of this increasing awareness of therapeutic nuclear medicine. It is the time to act and provide the necessary impetus to this ever expanding branch of nuclear medicine. It is expected that meaningful discussions will be held in Cyprus during the conference and a solid road-map be created for the growth and development of radionuclide therapy in a global scale.This supplementary issue of the World Journal of Nuclear Medicine contains most of the abstracts of scientific papers and invited lectures to be presented at the ICRT-2005. The abstracts have been edited and formatted to the extent considered necessary for readers' assistance. The views expressed/ implied and the general style adopted remains however, the responsibility of the authors. I have really enjoyed immensely organizing this conference as its scientific secretary and I hope that we are going to have a wonderful time in Limassol celebrating ICRT-2005.

Ajit Kumar Padhy

S-2

Scientific Programme

Monday: 10 October 2005

Tuesday: 11 October 2005

Time Abstract Title of Presentation AuthorsNo.

0900-1600 Registration, as participants start arriving in Cyprus

1900-2200 Pre-conference get-together

0800-1600 Registration

0900-1030 Scientific Session-I: General

Chairpersons: Hoefnagel C (The Netherlands), K. Kouris (Cyprus)

USA-114 Future Directions in Bone-Localizing Srivastava S Therapeutic Radiopharmaceuticals

USA-112 Therapeutic Applications of Rhenium- Knapp, Jr., F. F. 188 in Nuclear Medicine and Oncology - (Russ) Current Status and Expected Future Perspectives

USA-117 Advances in targeted radioisotope Divgi C therapy in cancer.

1030-1100 Tea/ Coffee

1100-1300 Scientific Session-II: Thyroid-1Chairpersons: San Luis TOL (Philippines), J. Kropp (Germany)

UK-105 Radionuclide therapy of S. Vinjamuri Hyperthyroidism: An over view

RSA-085 Treatment of Hyperthyroidism with Ellmann A Radioiodine: comparison of the efficacy of low, medium and high doses of I-131,with special emphasis on the socio-economic issues related to the treatment

PHI-072 Therapeutic Options in the Management Barrenechea E et al. of Autonomously Functioning Thyroid Adenomas.

CZR-021 Our experience with radioiodine therapy Kraft O of thyroid functional autonomies

LAT-059 ¹³¹I therapy for euthyroid goitre in Berzina A et al. Latvia.

MAL-063 Role of antithyroid drug treatment prior Das BK et al.to radioiodine therapy in hyperthyroidism

IND-046 Incidence of micronuclei as biological Senthamizhchelvan dosimetry in differentiated thyroid S et al. carcinoma patients treated with 131I

SLO-095 Recombinant Human TSH (rh TSH)- Schwarzbartl-Pevec aided radioiodine therapy in patients A et al. with differentiated thyroid carcinoma: Results 2002-4

Programme

S-3



Posters: Brief Reports

BOH-123 Effect of radioiodine therapy on thyroid Rajkovca Z et alnodule size in patients with toxic adenomas

BGD-010 Design & Development of a Lead Jar for Rahman Miah S et oral administration of radioiodine in al. hyperthyroid patients.

IRA-052 Comparative Evaluation of the Two Esfahani AF et al.Fixed Dose Methods of RadioiodineTherapy (185 MBq and 370 MBq) for the Treatment of Graves' Disease.

SER-087 Is drug-free period prior to radioiodine Han R et al. therapy decisive for treatment outcome in patients with multinodular toxic goitre?

POL-078 A Retrospective Assessment of the Budlewski T et al. Effectiveness of Radioiodine Treatment of Hyperthyroid Patients from 1997 to 2003 in the North-Eastern Region of Poland.

IND-048 Radioactive iodine (I-131) in treatment Sood A et al.of hyperthyroidism in Hilly Terrain Initial Experience.

BGD-011 Radioiodine treatment for complicated Paul AK et al. hyperthyroidism using a fixed dose regime.

CPR-020 Study of the therapeutic dose and the Dang Y et al. clinical effect on Graves' disease with 131I treatment

LIT-060 Is it worth to calculate the dose of Mikalauskas V et al radioiodine?

BGD-007 Experience and outcome of radioiodine Rahman Miah S et therapy in hyperthyroidism al.

MON-064 Iodine-131 Therapy for the Treatment of Enkhtuya B et al. Hyperthyroidism

1300-1400 Lunch

1400-1600 Scientific Session-IIISolid Tumour and Miscellaneous TherapyChairpersons: B.A. Krishna (India), F.F. Knapp (USA)

UK-103 Radiolabelled Aptamers for tumour A. Perkinsimaging and therapy

UK-100 Problems with antibody treatment of solid tumours Buscombe J GER-032 Intracoronary radiation therapy: Placebo Kropp J

controlled study A Report. URU-111 Intravasular Radionuclide Therapy to Alonso O et al.

prevent restenosis following PTCAJAP-057 Effect of Auger Electrons Internalized as Watanabe N et al.

Indium-111 Labelled N-MYC Phosphorothionate Antisense Oligonucleotide(In-111-N-MYC-AS) on Human NeuroblastomaCells: In vitro and In vivo studies

S-4


Programme



IRA-056 Dose calculations of 186Re for Taghizadeh-asl M etproduction and feasibility of use to al. intravascular brachyherapy after coronary Angioplasty

POR-082 Therapeutic Radiopharmaceuticals Neves M et al.UK-106 Radioimmunotherapy of Pancreatic S. Vinjamuri

cancer with monoclonal antibodiesBGD-006 Studies of therapeutic effects of Beta- Afroz S et al.

radiation on Onchomycosis. IND-039 188 Re(V)DMSA -PLGA micro-spheres Shukla J et al.

for targeted therapy of neurogenic tumorsGRE-034 Labeling of a Bombesin analog with Koumarianou E et

Rhenium-186 al.IND-050 A single vial method of preparation of I- Snehlata et al.

131 MIBGIND-051 Tele consultation and tele follow up of Pradhan PK et al.

thyroid cancer patients A pilot studyPOL-079 Intravascular radionuclide therapy using Birkenfeld B et al.

Re-188 Perrhenate to prevent re-stenosis following PTCA: Initial Experience in Poland

SLO-096 Another case of metastatic malignant Žagar I et al. Struma Ovarii? A case report of good response to radioiodine therapy.

UKR-108 Radionuclide therapy of true Afanasieva NI et al. polycythaemia

SER-088 32-P Orthophosphorus in the Treatment Jaukovic L et al.of Polycythaemia Vera and Essential Thrombocythaemia

BGD-013 Post-operative beta-irradiation in the Jehan AH et al. management of pterygium

BGD-012 Use of strontium-90 beta irradiation as Nisa L et al. an adjunctive therapy for the management of squamous cell carcinoma of the conjunctiva

POL-080 Sentinel Lymph node mapping and Birkenfeld B et al.detection in patients of melanoma: Role in prognosis

PHI-076 Incremental value of nitrate Duldulao M et al.enhancement in Tc99m Sestamibi myocardial perfusion imaging with SPECT in patients with coronary artery disease and previous myocardial infarction

AZB-005 Distant gammatherapy results of patients Shiraliyev OK et al.with esophagus cancer

S-5


Programme


1600-1730 Scientific Session-IV: Thyroid-2Chairpersons: A. Perkins (UK), A. Staudenherz (Austria)

CZR-023 International cooperation in the Kraft O et al.treatment of patients with differentiated thyroid cancers.

IND-047 Optimizing the indications for Choudhury PS et al. radioiodine therapy as an adjuvant treatment in differentiated thyroid carcinoma.

CPR-019 Retinoic acid in patients with Zheng R et al.radioiodine non-responsive differentiated thyroid carcinoma.

ROM-083 Radioiodine therapy of differentiated Gherghe M et al. thyroid cancer in patients with negative diagnostic I 131 scintigraphy and high serum thyroglobulin level

IND-043 Treatment of differentiated thyroid Krishna BA et alcancer using Recombinant TSH injection

AUS-004 Statins As A New Therapeutic Approach Hofmann A et al. In Dedifferentiated Thyroid Cancer? A Case Report

PHI-075 Prospective Randomized Trial for the Barrenechea EA et Evaluation of the Efficacy of Low Vs. al.High Dose I-131 for Post Operative Remnant Ablation in Differentiated Thyroid Cancer

BUL-016 99mTc-MIBI and 131I scintigraphy in the Sergieva S et al. follow-up of differentiated thyroid carcinoma(DTC) patients after surgery.


PHI-073 The Value of PET in DTC with Barrenechea EA et Negative WBS but Elevated al.Thyroglobulin levels

IRA-055 Study of ablation efficiency of 3600 Takavar A et al.MBq of I-131 in the Treatment of Thyroid Carcinoma

UKR-107 Sialoscintigraphy with 99m Tc- Korol P pertechnetate in evaluation of salivary gland function in patients with differentiated thyroid cancer after radioiodine therapy

IRA-053 The Rate of Depression and its Risk Eftekhari M et al.Stratification in Patients With Differentiated Thyroid Cancers Treated With Radioactive Iodine

BGD-008 Success of Repeated I-131 Therapy in Alam F et al cases of Metastatic Differentiated Thyroid Carcinoma

S-6


Programme


Wednesday: 12 October 2005

Thursday: 13 October 2005

IND-040 Our experience with the treatment of Anand YNI et al. 155 cases of carcinoma of the thyroid

IND-049 Evaluation of medullary carcinoma Krishnakumar Rthyroid.

IND-044 Our Experience of High Dose I-131 Dougall P et al. Therapy in 75 patients with Well Differentiated Carcinoma Thyroid Followed Up Over 5 years

UKR-109 Up to date programme of treatment and Afanasieva NI et al. long-term follow-up of the patients withdifferentiated thyroid carcinoma

PER-071 Influence of T-3 produced by metastatic Mendoza G et al. thyroid tissue on I-131 treatment outcome.

BGD-014 Second malignancies following the Yashmin S et al. treatment of differentiated thyroid carcinoma with radioiodine

SRL-097 Radioiodine (I131) application in the Nanayakkara D management of differentiated thyroid cancer (DTC) Audit

IND-045 Air Monitoring in Radioiodine Therapy Sarika et al. Ward

1900 Opening CeremonyFollowed by: Gala Dinner

0800-1200 Pre-lunch Guided educational tourof Cyprus

1200-1400 Lunch at a Fish Taverna

Scientific Session-V

Luncheon Meeting : Special Session on WRPTCChairpersons : Turner H (Australia), S. Srivastava (USA)Brainstorming : WRPTC: How to proceed from here,

New Ideas, Future Directions (All Participants)

1400-1800 Post-lunch Guided educationaltour of Cyprus

0830-1030 Scientific Session-VI: Bone Pain Palliation & MiscellaneousChairpersons: A. Ellmann (S. Africa), E. Barrenechea (Philippines)

USA-118 The role of imaging in planning therapy C. Divgi in cancer.

S-7


Programme


UK-104 C-595 Antibody: A potential vector for A. Perkins targeted alpha therapy

GER-028 Radionuclide therapy in palliative Liepe K treatment of metastatic bone disease: Review

IND-038 Sm-153 EDTMP therapy for bone pain Tripathy M et al palliation in skeletal metastases: AIIMS Experience.

PAK-068 Formulation and evaluation of Beta- Muhammad S et al emitting radionuclide labelled EDTMP for bone pain palliation.

ROM-084 Use of Sr-89 for bone pain palliation: Mititelu R et al. Experience in our department.

PER-070 Impact of educational strategies in Seminario C et al. positioning Samarium-153 EDTMP as atreatment for pain due to bone metastases.

LIT-062 Bone pain palliation with strontium-89 Tiskevicius S et al in cancer patients with bone metastases

GRE-036 Comparative Study of Skeletal Papanikolos G et al. Dosimetry Methods in Therapeutic Schemes with Re186 HEDP and Sm153 EDTMP


POL-081 188W/188Re generator as a convenient Mikolajczak R et al.source of 188Re perrhenate solution and a kit for preparation of 188Re-HDEHP

IRA-054 Strontium-89 in Palliative Treatment of Haddad P et al.Widespread Painful Bone Metastases: Response Rate and Duration

UKR-110 Combination Radiation Therapy for Afanasieva NI et al. Bone Metastases in Thyroid Cancer

SLO-093 Radionuclide Therapy in Slovenia Fettich JDOM-024 Radiopharmaceutical Therapy in de los Santos JO

Dominican Republic. Present and FutureUZB-121 Nuclear Medicine in Uzbekistan & Rasulova N et al.

Current status of Radionuclide therapy in the country

EGY-025 Osteosarcoma target therapy with stem Fawzy A cell transplant A case review

1030-1100 Tea/ coffee

1100-1300 Scientific Session-VII: RadiosynovectomyChairpersons: AH Elgazzar (Kuwait), P. Bernal (Colombia)

GER-030 Radiosynovectomy; A Review Liepe K VEN-122 Radiosynoviorthesis Fernando Palazzi F BRA-015 Use of Samarium 153 Hydroxyapatite Anselmi OE et al.

for intra-articular therapy

S-8


Programme


PHI-074 Comparative evaluation of the efficacy Barrenechea EA et of radiosynovectomy with conventional al. intra-articular therapy in rheumatoid arthritis and haemophilic arthropathy (CERAHA)

ALG-001 Use of radiosynoviorthesis with Y-90 in Bouyoucef SE et al. the treatment of Persistent knee hydarthrosis

SLO-094 The Efficacy of Radiosynoviectomy in Grmek M et al. Hemophilic Hemarthrosis According to the Frequency of Joint Bleedings

IND-037 Radiation synovectomy versus intra- Solav S articular steroid treatment in inflammatory arthritis


MON-066 Radiation synovectomy with 188Re-tin Erdenechimeg S et colloid in histological study al.

ARG-002 Two-year results of radiosynovectomy Soroa V et al in knee-joints of Hemophilic patients using locally developed P-32 colloid.

SLK-092 Evaluation of the Efficacy of Vereb M et al. Radiosynovectomy in Rheumatoid Arthritis and Haemophilic Arthropathy (CERAHA): First Results of an IAEA Co-ordinated Research Project (CRP)

EST-026 Radiosynovectomy: first results in Nazarenko S et al. Estonia

CZR-022 Our experience with radiosynoviorthesis Kraft O et al. and re-radiosynoviorthesis of knees.

IND-041 Comparison of musculoskeletal USG Ray S et al. and radionuclide soft tissue scintigraphy in the evaluation, selection and follow-up of patients for radiosynoviorthesis

1300-1400 Lunch

1400-1600 Scientific Session-VIII: Lymphoma/ Other Haematological Malignancies and Liver CancerChairpersons: H. Amaral (Chile), J. Buscombe (UK)

USA-120 Role of Radionuclides in Therapy of Wiseman G Haematologic Malignancies.

SIN-091 Radioimmunotherapy of Refractory B- Sundram FX Cell Lymphoma

GER-033 Radionuclide Therapy of B-NHL with Kropp J 90-Y-Epratuzumab: A report of the multi-centre trial

AST-003 I-131 Rituximab (chimeric anti CD 20 Turner JH Mab) radioimmunotherapy of non-Hodgkins lymphoma

S-9


Programme


IND-042 Impact of FDG-PET imaging in the Krishna BAtreatment of Lymphomas: Indian experience

UK-101 Radionuclide treatment of Liver Cancer Buscombe JHusing I-131 Lipiodol A review

UK-102 Use of Y-90 lanreotide and Y-90 Al-Nahhas Amicrosheres in treatment of liver tumours.

SIN-090 Experimental therapy with P-32 for Goh A et al. hepatoma

COL-018 Radionuclide treatment of Liver Cancer Bernal P et al. using Re-188 Lipiodol


PAK-069 Trans-Arterial Radioconjugate Asghar S et al. Radionuclide Therapy For Hepatocellular Carcinoma; Feasibility & Applications In Pakistan

PHI-077 Radionuclide treatment of Liver Cancer San Luis TOL et al. using Re-188 Lipiodol: Experience in Philippines

SER-086 Possible Role of the Scintigraphic Artiko V et al. Estimation of the Relative Liver Perfusion in the Choice of Treatment of Liver Carcinomas.

SIN-089 [Re(CO)3]-Chelates as Therappeutic Saw MM et al. Radiopharmaceuticals for the treatment of Hepatocellular Carcinoma

MON-065 Treatment of HCC with Re-188 lipiodol Erdenechimeg S Initial experience in Mongolia

THA-098 First Experiences in 90Y-Zevalin For Saesow N et al.Treatment of Non-Hodgkin's Lymphoma in Thailand.

1600-1730 Scientific Session-IX: Neuro-endocrine TumoursChairpersons : M.C. Lee (Korea), V. Soroa (Argentina)

UK-099 Pathophysiology and non-radionuclide therapyof neuroendocrine tumours Buscombe J

GER-029 Peptide Receptor Radionuclide Therapy Baum R (PRRT) of Neuroendocrine Tumors Using Y-90 and Lu-177 Labeled Somatostatin Analogs: Principles, Technique and Clinical Results after 500 Treatments

NET-067 Interventions in 131I-MIBG treatment of Hoefnagel CAneuroendocrine tumours

GRE-035 Patient specific dosimetry of I-123 Lyra M et al. MIBG in diagnosis for improvement of dose estimation in I-131-MIBG adrenal tumours therapy

S-10


Programme


Friday; 14 October 2005

GER-031 Peptide Receptor Radionuclide Therapy Wehrmann C et al. (PRRT) of Neuroendocrine Tumors: First Comparative Results using the Somatostatin Analogues Lu-177 DOTA-NOC and Lu-177 DOTA-TATE

Posters: Brief reports

CHI-017 Peptide receptor radionuclide therapy Amaral H with Y-90 DOTATOC (Somatostatin analogue) in neuroendocrine tumours: The Chilean Experience

LIT-061 Somatostatin receptor imaging and Kulakiene I et al. therapy an ever expanding choice

EST-027 Our first experience in the application of Samarina G et al. 131I-MIBG in a patient with neuroblastoma (case report).

BGD-009 Targeted therapy of neuroblastoma with Hussain R et al.I131 -MIBG: experience of 15 cases.

1930 Dinner & Cyprus Night

0830-1030 Scientific Session-X : Development of new radiopharmaceuticals, Intracellular targeted therapy and Molecular Imaging in Radionuclide TherapyChairpersons: Baum R (Germany), Nazarenko S (Estonia)

USA-113 Therapy with High LET Radioisotopes Knapp, Jr., F. F. Can Sufficient Levels of Attractive (Russ) Auger and Alpha Emitters be Produced to Make Their Use Practical?

USA-116 Development and Evaluation of High Cutler CS et al Specific Activity Radioisotopes for Radiotherapy

KOR-058 Role of PET for monitoring the Lee MC therapeutic response

USA-119 Incorporating FDG PET Imaging in the Wiseman G Response Criteria for Non-Hodgkin's Lymphoma

USA-115 Radiolabeled Adenoviral Sub-Unit Srivastava S Proteins for Molecular Imaging and Therapeutic Applications in Oncology

1030-1130 Closing

S-11


Programme

001-ALGUse of Radiosynoviorthesis with Y-90 in the Treatment of Persistent Knee Hydarthrosis

1 2 3 3Bouyoucef SE , Henni-Haddam F , Sellah M , Aouli S , 1 1 3 2Benlabgaa R ,Hanzal A , Mansouri B , Abtroun S ;

1Department of Nuclear Medicine, CHU Bab El Oued, Algiers; 2Department of Rhumatology, CHU Bab El Oued, Algiers; 3Department of Radiology, CHU Bab El Oued, Algiers, Algeria

002-ARG:Two-year Results of Radiosynovectomy in Knee-joints of Hemophilic Patients Using Locally Developed P-32 Colloid. Soroa V, Velázquez Espeche MH, Giannone C, Caviglia H, Galatros G, Nicolini JO Centro de Medicina Nuclear, Comisión Nacional de Energía Atómica Argentina, Buenos Aires, Argentina; Traumatology & Orthopedics, Htal. Municipal J. A. Fernández, Hemophilic Foundation, Buenos Aires, Argentina; Radiopharmacy, Lab. Bacon, Buenos Aires, Argentina.

The objective of this study is to determine the treatment success rates and factors predicting successful outcome when using yttrium-90 intra articular injections as treatment of persistent knee hydarthrosis refractory to other treatments. 68 patients, 41 with rheumatoid arthritis, 9 with ankylosing spondylarthritis, 6 with Behcet disease, 6 with psoriatic arthritis, and 6 patients with gonarthritis, with a total of 121 knees have been treated by Yttrium 90 (Y90) for a persistent hydarthrosis. Mean duration of the knee effusion was 4.85 years(range 1 to 20 years) and mean number of intra articular steroid injection was 3.85 (range 1 to 20 steroid injections). According radiological classification of Steinbrocker, 68 knees were in stage I and 53 were in stage 2. Pain, mobility, volume effusion and needs to further intra articular steroid injection were the main parameters to evaluate the outcomes of the radiosynovectomy. Outcomes were assessed for each patients as 'excellent improvement', 'good improvement', 'fair improvement' or 'not improved' by review of the case notes at 3, 6,12,18,24 months. Excellent and good outcomes were equal to 63.2% at 3 months, 66% at 6 months, 65.9 % at 12 months, 59% at 18 months and 53% at 24 months. By aetiology, best score, for excellent and good outcomes, was observed for Behcet disease(100% at 12 and 24 months) and for rheumatoid arthritis (83% at 6 months). Best outcomes were also obtained when knees are classified at radiological stage 1 ( 66% at 6 and 12 months) and when knee effusion duration is inferior to 2 years ( 78% at 12 months). No significant improvement was observed for knees at stage 2 and ankylosing spondylo-arthritis (49% with no improvement at 6 months). Radiosynoviorthesis treats successfully patients with persistent knee effusion refractory to other therapies. Patients with Behcet disease and rheumatoid arthritis, less destructive radiographic changes, shorter duration of joint disease, tend to respond more favourably and have good outcomes.

The aim of this study was to assess the effects of radionuclide treatment of haemophilic arthropathy of knee joints refractory to conventional medical therapy with the locally developed P-32 colloidal suspension in Argentina, and compare the results with those of chemical synovectomy, and to assess the cost/ effective aspects of radiosynovectomy. It may be noted that other imported colloidal radiopharmaceuticals like Y-90 citrate, Re-186 sulfide or Er-160 citrate are expensive in Argentina. On the other hand we have the technology to prepare Ho-166 macro-aggregates in Argentina, but the radiopharmaceutical has not been approved for use on humans by the

country's regulatory authorities.Radiosynovectomy was performed using P-32 colloid in 58 male

hemophilic patients, ages ranging from 4-52 years. Nine patients had re-treatments either in the same or in the contralateral knee, making it a total of 67 procedures in the study. In adults, a dose of 37-74 mCi was used, while 33% of this dose was used in children between 2-6 years, 50% in children between 6-10 years and 75% in children between 10-16 years of age. Patients with Grades II & III arthropathies were included in the study. Informed consents from adults and from the parents of children were obtained. Patients with large Bakers cyst, grade IV arthropathy, infection in the skin around the joint area and bleeding at the time of the procedure were excluded from the study. Documentation clinical history and AHF therapy was done in all cases. All patients underwent three phase bone scans before therapy and after therapy at 1, 3 6, 9 and 12 months. If required, joint aspiration was carried out. P-32 Bremsstrahlung emission was used in the scintigraphies for early and late imaging to confirm the presence or absence of leakage. All patients were subjected to immobilization of the treated joints and relative rest for a period of 72 hours following therapy.There were no local or systemic adverse effects following treatment. No leakage of radioactivity was detected in any of our patients. Intraarticular Rifampicin procedure required frequent injections. The follow-up evaluation demonstrated significant improvement of joint motion, diminished knee volume and less requirement and frequency of the use of Anti-haemophilic Factors (AHF) in 80% of patients subjected to radiosynovectomy (54 /67 procedures), thus lowering treatment costs. Remission Indices (rate of change of lesion activity over time) calculated over the treated joints using sequential Tc-99m MDP soft tissue scintigraphy revealed significant reduction of lesion activity objectively.Overall it has been observed that one intra-articular knee radiosynovectomy procedure using P-32 colloid in patients with haemophilic arthropathy could provide relief from symptoms for a period of 3-6 months. We have found radiosynovectomy to be safe and cost-effective and recommend its use as an alternate therapeutic procedure where availability of AHF is difficult and expensive.

Commercially available anti-CD 20 monoclonal antibody, rituximab (MabThera®) may be efficiently radioiodinated with 131I using standard Chloramine-T methodology in a hospital radiopharmacy, under appropriate regulatory authority approvals. Multicentre clinical trials of 131I-rituximab radioimmunotherapy have been performed in patients with relapsed or refractory low grade non-Hodgkins lymphoma with therapeutically effective administered activities being determined on the basis of individualised prospective patient dosimetry. A non-myeloablative regimen of 131I-radioimmunotherapy predicated upon a maximum prescribed dose of 0.75 Gy to whole body has been used to minimise myelotoxicity in patients undergoing radioimmuno-therapy, even when they have been heavily pretreated with chemotherapy and/or there is tumour infiltration of bone marrow greater than 25%. Provided that baseline leucocytes exceeded an absolute neutrophil count of 1.5 x 109/L and platelets > 100 x 109 /L, the incidence of grade IV haematological toxicity was 16% for neutrophils and 4 % for

003-ASTI-131 Rituximab (Chimeric Ant i Cd 20 Mab) Radioimmunotherapy of Non-Hodgkins LymphomaTurner JH, The University of Western Australia, Fremantle Hospital, Alma Street, Fremantle WA 6160 Australia

S-12


Abstracts: ICRT-2005


platelets which was self-limited. The red marrow radiation absorbed dose in selected patients receiving 131I activities estimated to deliver 0.75 Gy to whole body was calculated to be less than 2 Gy using Monte Carlo methodology on post therapy CT/SPECT imaging. Predictive dosimetry was performed by serial whole body imaging following IV administration of a standard 200 MBq 131I-r i tuximab tracer and determination of individual pharmacokinetics of the radiolabelled antibody in each patient. A standard dose of 375 mg/m2 unlabelled rituximab (MabThera®) was administered IV immediately prior to the tracer and therapy doses of 131I-rituximab to minimise nonspecific uptake of the radiolabelled antibody and to optimise the tumour to background activity. The administration of a standard course of 4 cycles of cold rituximab (MabThera®) in association with the prescribed maximum ac t iv i ty o f 131I - r i tux imab cons t i tu tes radioimmunotherapy rather than antibody-targeted internal radiotherapy. Such treatment in 90 patients with relapsed/refractory follicular (grade I, II, III) (78) MALT (5) and small lymphocytic (7) lymphoma with 3 (1-8) median prior chemo-therapies, 60% stage III/IV, resulted in complete remission (CR) in 51% and partial response (PR) in 23% for an overall response rate (ORR) of 74%. In contrast to radiolabelled murine antibodies, the 131I-rituximab chimeric monoclonal antibody does not cause any immunogenic HAMA host response and repeated courses of 131I-rituximab radioimmunotherapy may be given for subsequent relapse. The median duration of response was 22 months in our patients who achieved CR and retreatment was performed in 8 patients, the majority of whom responded again to the repeat 131I-rituximab radioimmunotherapy. Median progression-free survival in our patients was 13 months and the 4 year actuarial survival of all our treated patients after 131I-rituximab radioimmunotherapy for non-Hodgkins lymphoma was 63%.Non-myeloablative radioimmunotherapy of mantle cell non-Hodgkins lymphoma with 131I-rituximab showed CR in 2 of 8 patients, but the reported results of myeloablative regimens and autologous stem cell rescue demonstrate CR in 6 or 7patients after 131I-rituximab treatment. Indolent non-Hodgkins lymphoma which transforms into more aggressive forms may also be treated with a myeloablative regimen combining standard dose 131I-rituximab radioimmunotherapy with BEAM chemotherapy for conditioning prior to stem cell autograft at 16 days. Three patients with transformed non-Hodgkins lymphoma treated with 131I-rituximab, BEAM chemotherapy and stem cell rescue all achieved CR of duration of at least 12 months. Refractory or relapsed aggressive non-Hodgkins lymphoma such as DLCBL may also be treated with nonmyeloablative protocols complemented by long-term consolidation and maintenance MabThera immunotherapy, currently in clinical trial. Greater experience has been obtained with 131I tositumomab (Bexxar® ) in both marrow sparing radioimmunotherapy of relapsed and first line treatment of low grade non-Hodgkins lymphoma and in myeloablative protocols of radioimmunotherapy of aggressive or refractory non-Hodgkins lymphoma with bone marrow transplantation. This clinical experience with radioiodinated murine anti CD 20 Mab radioimmunotherapy will be compared with that of 131I-rituximab chimeric antibody radioimmunotherapy of non-Hodgkins lymphoma.

004-AUSStatins As A New Therapeutic Approach in Dedifferentiated Thyroid Cancer?A Case ReportA. Hofmann, P. John, M.P. Schaffarich*, H. Sinzinger, A. StaudenherzUniv. Clinic of Nuclear Medicine, Medical University of Vienna, Austria & *Centre for Biomedical Engineering and Physics, Medical University of Vienna

005-AZBDistant Gammatherapy Results of Patients With Esophagus Cancer.Shiraliyev O.K., Beibutov Sh.M., Quilieva A.O., Nasirova F.J.Dept. of Nuclear Medicine, Republic Diagnostic center & Azerbaijan, Dept. of Nuclear Medicine, National Cancer Centre, Azerbaijan

In general differentiated thyroid tumours are removed surgically and afterwards treated with radioiodine. However, still about one third of patients with differentiated tumours, metastasise. Also 30 percent of recurrent thyroid carcinomas do not respond to iodine treatment due to loss of differentiation. Retinoic acid, biological metabolites of vitamin A, are considered to induce re-differentiation of the thyrocyte and thereby induce tumor regression. In follicular carcinoma cells, it also plays an important role in inducing iodine uptake. Retinoids, however, cannot be used in liver disease as they may induce hepatic enzyme increase. In

addition 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are reported to induce on the one hand cellular apoptosis and on the other hand, in a lower dosage, differentiation in anaplastic thyroid carcinoma cells in vitro. We are presenting a 79 years old female patient with an oxyphilic follicular thyroid carcinoma and histologically verified autoimmune hepatitis. The first posttherapeutic scan, showed only focal cervical localized ioidine uptake. Also 3 months later no pathologic iodine uptake was recognized on the diagnostic scan, whereas the FDG-PET showed solid uptake of FDG cervical, in both lungs, in the mediastinum, the pelvis and the right hip. Due to contraindication for retinoic acid the patient was treated with usual dose statin for about 4 weeks to induce re-differentiation. Following, the patient was administered 9,25 GBq I-131 again and the posttherapeutic scan showed iodine uptake cervical and in the right femur. We conclude that the administration of Statins, at low dose (20 mg/day) even over a short period of time, only may induce re-differentiation as well as an antiproliferative effect in vivo

The problem of esophagus cancer therapy gains the particular meaning for Azerbaijan where this disease incidence exceeds the parameters of neighboring countries by almost two times. 1240 patients with esophagus cancer were under our observation for more than 15 years who had been subjected to the distant static gamma therapy on apparatuses “Agat-R” and “Rockus M”. there were 732 men (59 % )and 508 women (41 %) . The patients' age ranged from 24-88 years. Disease duration since the appearance of the first symptoms till entering to the department was 4-8 months on the average.Esophagus cancer is often localized in the places of the physiological stenosis. So tumour was lacalised in the neck region esophagus in 45 patients (4.1%), in upper pectoral in 104 ones ( 9.5%), in middle pectoral in 594 ones (54.5%) in lower pectoral in 299 ones (27.4%) in abdominal regions of esophagus 48

S-13


patients(4.5%).The extent of dimensions of tumour esophagus was ranged within 2-13 cm, only it was less than 5 cm in 6.5% patients.The opportune surgical treatment ensures the perfect recovery. However, the early stage of the disease can develop

stasymptomatically. The patients with the 1 stage of lesion were nd rdonly 8 (0.8%) with the 2 one 408(37.4%), with the 3 one

th607(55.7%), with the 4 one 67(6.1%). Radiation therapy was applied in the cases of inoperable and also in patient who were older than 60 or refused operation. 1090patients (88%) finished the treatment course. Local summary doses have formed 50-70 Grey , the momentary ones-2-2.5 Grey on the medium. The rest of the patients haven't finished the treatment due to several reasons. The results of the treatment are as follows: We observed clinical cure in 389 patients (35.7%) , an improvement in 541 (499%), the process stabiliation or an absence of effect in 160 (14.3%). 40.1% of patients lived for more than 1 year, 18.4% for more than 2 years,12.0% for more than 3 years and 7.0% for more than 5years. It was established that the best results were obtained in case of tumour location in the middle and lower regions of esophagus. We concluded that radiation has a palliate effect with the temporary stabiliztion, partial or nearly complete regression of tumour in most patients and saves a lot of patients suffering from the severe symptoms. Radiation treatment of esophagus cancer is recommended as a routine in oncological establishments.

Onychomycosis is the most frequent cause of nail disease and the most prevalent type of dermatophytosis in Bangladesh. The humid and warm climate of this tropical country is congenial for the growth of fungi. Therapeutic limitations of conventional antimycotic agents in respect of low cure rates, high relapse rate, inherent side effects, long duration of treatment and high cost in treating onychomycosis have provided clear incentives to explore alternative forms of treatment procedure. The objectives of the present thesis work were:(i) To use beta radiation as a curative therapy for

Onychomycosis, optimisation of its dosages and to promote an innovative clinical development in the field of therapeutic application of nuclear medicine

(ii) To assess the efficacy of beta radiation either alone or in combination with conventional antifungal therapy; and

(iii) To reduce the duration of drug exposure and cost of treatment for onychomycosis.

This is a PhD research work under the University of Dhaka and was sponsored by the Ministry of Science and Information & Communication Technology, Government of the people's republic of Bangladesh. This study is an open, randomised and controlled trial to verify the efficacy of beta radiation in patients with onychomycosis. Using the appropriate statistical formula, sample size of the study population was determined and in each group 92 patients were assigned. With an assumption of patients drop out and for better statistical analysis, a total of 330 patients, who fulfilled the inclusion criterion having diagnosed to have onychomycosis clinically and mycological were randomly allocated to enter in therapeutic regimen. Study population was

006-BGDTherapeutic Effect of Beta Radiation on Onychomycosis an Innovative TreatmentAfroz S, Islam N, Rashid H, Shahidullah M, Ali S, Islam S K M, Hossain S, Ali NCentre for Nuclear Medicine & Ultrasound, Dhaka Medical College Hospital, Dhaka-1000, Bangladesh

randomised in three groups. Group A (n =110) received griseofulvin orally 500mg once daily for 12-16 weeks; Group B (n=110) received beta radiation, 500 rads bi-weekly for 3 weeks (total 2500 rads); and Group C (n=110) received combined beta radiation (total 2500 rads in 3 weeks) and griseofulvin (500 mg daily for 6 weeks). Patients were followed up for 24 weeks. Efficacy of the treatment was evaluated in all 287 patients while 43 (13.03%) cases were dropped out from the initial allocation. At the end of the follow up period (6 months after discontinuation of treatment) mycological cure rate was achieved 41 (42.70%), 36 (38.70%) and 65 (66.33%) in Group-A, Group-B and Group-C respectively. The mycological cure rate was highly significant (P=0.000) and considered to be the acceptable outcome of treatment. Clinical cure rate was considered as another way of assessment. Percentage of clinical cure rate was similar as mycological cure rate and equally significant (P=0.000). Recurrence rate of the disease was highest in griseofulvin-induced patients 21 (21.88%) and in beta radiation exposed patients was 14 (15.06%). This rate was least in combination therapy group of griseofulvin and beta radiation 4 (4.08%). Cure rate in Group C is significantly higher than Group A and B as well (P=0.000). Several known side effects causing systemic involvement of oral drugs are already being experienced, side effects like blackening of surrounding soft tissue of nail were observed which were transient and self-limiting. Further to this, all sample population underwent for biochemical and haematological tests pre and post radiation application. No significant change of tests results were observed excluding any observable radiation side affects to this particular type of radiation application.It can be concluded that the proposed new beta radiation treatment modality for onychomycosis exhibited a low risk- benefit ratio. It is well-tolerated and efficacious method to treat onychomycosis. From the observations of the present study it may be considered worthy to comment that in Group C as the cure rate is highest, recurrent rate is the lowest, duration and cost of treatment are significantly less, this modality of treatment can be considered as the more acceptable procedure for management of onychomycosis in a developing country like Bangladesh. Group B (beta radiation only) can also be accepted in special occasions to replace Group A (Antifungal). This innovative treatment procedure could be introduced in other Nuclear Medicine Centres of the country with a view to expand the procedure, so that large number of patients could be beneficiary as end users.

1Afroz S . Director, Centre for Nuclear Medicine & Ultrasound, 2Dhaka Medical College and Hospital (DMCH); Islam N .

Professor and Chairman, Department of virology, BSSMU, 3Dhaka; Rashid H . Principal Physicist, Centre for Nuclear

4Medicine & Ultrasound-DMCH; Shahidullah M , Professor and Head, Department of Dermatology and veneriology-DMCH, Ali

5S . Professor of Biochemistry, BSMMU & Member Public 6Service Commission, Islam S K M . Associate Professor, Dept. of

7 Microbiology, SSMCH, Hossain S . Associate Professor, Centre 8for Nuclear Medicine & Ultrasound-DMCH; Ali N . Biochemist,

Department of Bio chemistry-DMCH.

S-14



007-BGDExperience and outcome of Radioiodine Therapy in HyperthyroidismMiah SH, Paul AK, Rahman HACentre for Nuclear Medicine & Ultrasound, Khulna, Bangladesh

Radioiodine is being increasingly used in the treatment of hyperthyroidism. The primary reasons for choosing radioiodine therapy are its effectiveness, ease of administration, relatively low cost and paucity of side effects. Here we presented our experiences and outcome of radioiodine therapy in hyperthyroidism in a divisional referral centre.We retrospectively analyzed 203 patients receiving radioiodine therapy for hyperthyroidism in Centre for Nuclear Medicine & Ultrasound, Khulna during the period from July 1994 to June 2004. All the patients had clinical signs and symptoms of hyperthyroidism as well as elevated triiodothyronine (T ), thyroxine (T ) and suppressed thyroid 3 4

stimulating hormone (TSH). T , T and TSH were done in all cases. 3 4

Radionuclide scan and ultrasound of thyroid gland, radioactive iodine uptake (RAIU), thyroid microsomal antibody (TMAb) and fine needle aspiration cytology (FNAC) was done in selected cases. We assessed all patients prior to radioiodine therapy. Elderly patients and all those with cardiac complications and severe hyperthyroidism were pretreated with a short course of antithyroid drug in full dosages until they were clinically and biochemically euthyroid. Ninety five patients were on antithyroid medication (Neomercazole) prior to radioiodine therapy. Antithyroid medication were stopped 3 days before radioiodine therapy and restarted 3 days later and continued for 1 to 2 months depending on patient's symptoms. The rest of the patients received either no treatment or beta-blocker prior to radioiodine therapy. Menstrual history was taken in female patients and pregnancy was excluded by ultrasonography in doubtful cases before administering radioiodine. The likely consequences of the treatment were fully explained to the patients and attendants, the usual precautions for radiation protection of the public and the necessity of the follow-up were discussed and verbal consent was taken before administering radioiodine. Radioiodine was given

131orally as Na I solution to all patients in modified fixed dose regime ranged from 5 mCi to 15 mCi. All the patients were advised to attend the centre if any complications arise and in regular follow up at 6 weeks, 3 months, 6 months, 9 months and 1 year and then annually. Clinical and biochemical evaluations were done in follow up visit. If the first dose was found to be ineffective in controlling the disease or hyperthyroidism persist, then the second dose, third dose or fourth dose was given after 6 months interval with proper clinical and biochemical evaluation. If even with fourth dose, hyperthyroidism was not controlled, the case was referred for surgical management. The amount of radioiodine given in the second dose and in subsequent third dose or fourth dose was same as first dose or higher. Early complications of radioiodine were only encountered when the patient attended the centre for such. During follow up, patients were classified as cured if the functional status was either euthyroid or hypothyroid within 1 year without further treatment of hyperthyroidism by antithyroid drugs or radioiodine. Patient was diagnosed as hypothyroid on the basis of clinical and biochemical criteria, including low T and 4

high TSH. Total 203 patients with hyperthyroidism treated with radioiodine were studied. Among 203, 117 were female and 86 were male with female male ratio of 1.4:1. The mean age of the patients was 38.38 10.42 years (ranged 16 years to 70years). Among 203 cases, 190 (172 Graves' diseases, 8 solitary toxic nodule, 10 toxic multinodular goiter) patients attended regularly

as per advice and 13 patients were lost to follow up. It was found that 18 patients became euthyroid within 3 months, 35 patients became euthyroid within 6 months, 19 patients became euthyroid within 9 months and 97 patients became euthyroid within 1 year. Thus the cure rate was found to be 88.95% (169/190). In 18 (9.47%) cases hyperthyroidism persisted with no clinical and biochemical improvement within 6 months in which 15 were Graves' disease, 1 solitary toxic nodule and 2 toxic multinodular goiter. After becoming euthyroidism, hyperthyroidism recurs in 3 (1.58 %) cases within 1 year. Recurrence of hyperthyroidism was also seen in 2 cases after 1 year of radioiodine treatment. These patients (persistent and recur cases) were treated with second dose and if needed third and/or fourth dose of radioiodine. Second dose was given in 23 cases, third dose given in 7 cases and fourth dose given in 2 cases. We referred 1 case for surgical treatment not for responding even with fourth dose of radioiodine. During our follow up period, 6 patients became hypothyroid within 3 months, 14 patients became hypothyroid within 6 months, 7 patients became hypothyroid within 9 months and 5 patients became hypothyroid within 1 year. Thus hypothyroidism within 1 year was found to be 16.84% (32/190). Other side effects such as iododerma were observed in 5 (2.63%) cases, radiation thyroiditis developed in 17 (8.95%) cases, thyroid storm developed in 2 (1.05%) cases. Out of 43 with ophthalmopathy, 2 (4.44%) deteriorated, 1 (2.32%) unchanged and the rest (93.02%) improved. New ophthalmopathy developed in 3 cases (3/147 i.e., 2.04%). None developed any malignancy or leukemia during our follow up period. We conclude that our experience revealed similar outcomes as have been reported by other workers with the exception of iododerma, one of the early complications of radioiodine therapy that we noticed during our follow up period.

Differentiated Thyroid Carcinoma (DTC) is not an aggressive malignancy and its treatment is very promising. The treatment is performed by surgery only (in selective cases) or by surgery followed by I-131 therapy. Treatment of metastasis is equally effective but difficult in cases of lung and bone metastases. The objective of this study was to see the effectiveness of repeated doses of I-131 in cases of recurrence and metastasis. In this study we had evaluated 24 DTC cases who were given 5 to 13 doses of I-131 for ablation, recurrence and metastasis (in lymph node, lung and bone). The ages of the patients were between 18 to 70 years. These patients were given treatment in between 1982 to 1993 and were followed up for 12-22 years. It had been found that 6 cases out of 24 had bone metastases and all were follicular type of carcinoma except one who had mixed type. Not one of these cases was found completely disease free. Two patients were found scan negative in two consecutive scans, but again became scan positive. One patient died 10 years after detection of carcinoma after given 9 doses of I-131; another patient died 15 years after starting treatment with 13 doses. Another 2 patients had period of clinical improvement and deterioration that also got more than 8 doses. There were 4 cases of lung metastases (4 out 24) and only one had papillary carcinoma. Lung metastases were cured in 2 cases after 5 doses and was scan and Tg negative for 8 years; 2 cases of lung metastasis were in good clinical state but still they some

008-BGDSuccess of Repeated I-131 Therapy in Cases of Metastatic Differentiated Thyroid CarcinomaAlam F, Kabir MF, Karim MA. Institute of Nuclear Medicine, BAEC, BSMMU, Dhaka

S-15



recurrence even after having more than 8 doses. One of these patients is surviving for 17 years after disease detection with scan positive state.Recurrence of diseases in thyroid bed have good prognosis but these patients sometimes needed more than 5 doses to get relieve from recurrence. In our study among the 24 cases 6 patients needed more than 5 doses. Radioactive iodine was also not so effective in lymph node metastasis but surgical management is successful in most casesThis study showed that bone metastasis has least curative effect by I-131 and prognosis is worst. However, I-131 can still prolong life and it has also palliative effects in metastatic bone disease.

I-131 MIBG has been proven to be an effective therapeutic option in neuroblastoma targeted both at the primary tumor and its distant metastasis. We describe our initial experience in the targeted treatment of 15 patients with neuroblastoma. The patients were grouped and treated according to three protocols. Group 1: patients were in the advanced stage of the disease with either metastatic or unresectable disease; Group II: patients were treated immediately after diagnosis before surgery or any other management. Group III patients were treated with combined I-131 MIBG and high dose chemotherapy. The method of administration was by slow infusion (120min). Dose varied from 4 to 12 GBq in a single dose. All patients were followed up with periodic blood counts, liver and kidney function tests, thyroid and adrenal function tests. The response rate in group-I was 38%, group-II patients showed 52% and in group-III the overall response rate was 72.6%. Responses depended on high tumoral I-131 MIBG uptake and limited spread of the neoplasm. As regards toxicity, the major side effect observed was myelosuppression and this was found to be more severe in patients with bone marrow involvement and after chemotherapy. Toxicity was relatively mild in the neuroblastoma patients who were treated at diagnosis. There was no incidence of serious infections or significant bleeding in any of our patients. Extramedullary toxicity of hypothyroidism was observed in 1 patient. On the basis of the results, we can conclude that MIBG is an excellent pharmaceutical for the delivery of therapeutic doses of radioiodine for neuroblastoma. When combined with chemotherapy it is effective in obtaining a rapid response in heavily pre-treated patients who are resistant to other therapies.

Nuclear Medicine practices involve use of radioisotopes for diagnosis and treatment of diseases. Radioiodine is one of such radioisotopes, being used in the diagnosis and treatment of diseases since 1942. Handling of radioiodine involves radiation hazards both for the patients as well as for the technologists.

009-BGDTargeted Therapy of neuroblastoma with I-131 MIBG: Experience in 15 Cases. Hussain R, Nisa L, Karim MA Institute of Nuclear Medicine & Ultrasound, BSMMU, Dhaka,

Bangladesh;Centre for Nuclear Medicine & Ultrasound, Mitford, Dhaka, Bangladesh; Director, Bio-Sciences Division, BAEC, Dhaka, Bangladesh

010-BGDDesign & Development of a Lead Jar For Oral Administration of Radioiodine In Hyperthyroid Patients.Rahman MS, Paul AK, Rahman HA, Begum F. Centre for Nuclear Medicine & Ultrasound, Khulna, Bangladesh

Though radioiodine is supplied in a lead container, for treatment purpose, it is administered after dispensing into a glass jar that does not adequately protect radiation hazards. For this reason, we designed & developed a lead jar and radioiodine is dispensed into that lead jar to minimize radiation hazards. For oral administration of radioiodine to hyperthyroid patients, a lead jar was designed and developed with lead in Centre for Nuclear Medicine & Ultrasound, Khulna in December 2004 by own expertise and technologies in such a way that a glass jar could be introduced into that lead jar. The thickness of lead was 4.04 mm and the thickness of glass jar was 0.7 mm and thus the whole thickness of lead jar became 4.74 mm. The desired dose of radioiodine (8 mCi) that should be given to the patients were dispensed into that lead jar and administered orally to the patients. Radiation levels in 10 such cases were measured by Mini-Rad Series-1000 survey meter at 0.5 meter, 1 meter and 3 meters distances both lead jar and glass jar.The mean radiation level of lead jar and glass jar during oral

131administration of 8 mCi of Na I solution in 10 cases at 0.5 meter, 1 meter and 3 meters distances were 62.4± 1.96 microSv/h, 17.7± 1.95 microSv/h, 3.39± .12 microSv/h and 20.3± 2.16 microSv/h, 79.8 ± 0.79 microSv/h, 1.97 ± 0.23 microSv/h respectively. We have found that radiation level reduced by 67.47%, 61.58%, and 41.89% with lead jar at 0.5 meter, 1 meter and 3 meters distances. In conclusion, the locally designed and developed lead jar is safe, easy to handle and reduces radiation burden significantly in oral administration of radioiodine to hyperthyroid patients and recommended for routine practices in all nuclear medicine establishments.

011-BGDRadioiodine Treatment for Complicated Hyperthyroidism Using a Fixed Dose RegimePaul AK, Rahman SH, Ansari SM Centre for Nuclear Medicine and Ultrasound, Khulna, BangladeshCentre for Nuclear Medicine and Ultrasound, Bogra, Bangladesh

Hyperthyroidism in the elderly and all those with cardiovascular and psychiatric problem has increased mortality and morbidity rate. These patients need special care to cure the disease promptly and permanently for avoidance of complications. Radioactive I-131 is one of the accepted forms of treatment for hyperthyroidism and increasingly being considered for the patients in whom rapid and permanent control of disease is desirable. To evaluate the success of I-131 to cure disease in-patients with complicated hyperthyroidism, we prospectively studied the outcome of radioiodine therapy using a fixed dose regime. Ninety-three patients with toxic diffuse goitre (65 female, 28 male) age ranging from 29-67 years (mean ? SD 41.35 ? 11.02 years) were evaluated. The subjects included 71 cases with cardiovascular problem, 13 elderly patients, 5 with poor drug compliance and 4 with associated psychiatric disease. The individual was excluded from the study who had autonomous toxic nodule. Every patient was pretreated with antithyroid drugs for 4 weeks and the drug was discontinued for 3 days before administering I-131. No patients had post-treatment antithyroid drugs. All the patients were treated with a fixed oral dose of 15 mCi I-131 sodium iodide. Post-treatment follow-up examinations were done at 6 weeks without biochemical tests, at 3 months, 6 months, 9 months and 1 year and then annually with biochemical tests. Patients were classified as cured if the biochemical status was either euthyroid or hypothyroid at one year without further treatment by antithyroid drugs or radioiodine. Of the 93 cases, 82 patients became euthyroid or hypothyroid requiring no further treatment for

S-16



hyperthyroidism with an overall cure of 88.17%. Hypothyroidism was developed in 49 (52.69%) patients at one year of whom 39 became hypothyroid within 6 months and another 10 patients within 1 year. 4 patients were subclinical hyperthyroid at 6 months and still hyperthyroid at 9 months. 7 patients remained hyperthyroid 6 months after treatment. Thus, 11 (11.83%) patients remaining hyperthyroid 6 months following I-131 treatment and they were treated with a 2nd dose of 15 mCi I-131. No patient required more than two doses of I-131 in this study. In conclusion an initial dose15 mCi of I-131 is a simple, safe and effective means for the treatment of patient with complicated hyperthyroidism.

012-BGDUse of Strontium-90 Beta Irradiation as an Adjunctive Therapy For The Management of Squamous Cell Carcinoma of The Conjunctiva.Nisa L , Momta S , Jehan AH, Rahman MUCenter for Nuclear Medicine & Ultrasound, Mitford Hospital Campus, Dhaka.

013-BGDPost-Operative Beta-Irradiation in The Management of PterygiumJehan AH, Nisa L, Hossain R, Yasmeen S, Karim MACenter for Nuclear Medicine & Ultrasound, Mitford; Institute of Nuclear Medicine & Ultrasound; Director, Bio-Science Division, BAEC.

To evaluate the effectiveness of strontium-90 beta irradiation in management of squamous cell carcinoma of the conjunctiva. A retrospective analysis of the medical records of 5 patients treated with strontium-90 beta irradiation was done. Squamous cell carcinoma of the conjunctiva was histologically proved in all patients who had initial surgery to remove the major part of the lesion. This was followed by beta radiation within 48 hours with Sr -90 contact applicator obtained from Amersham International. The hand held Sr- 90 eye applicator was used after appropriately instilling the eyes with local anesthetics and a total of 5000cGy was delivered in seven fractions. Follow-up period was from 6 to 12months. Clinical response and side effects to the therapy were used as outcome measurements. Three patients showed good response with no evidence of tumor within 6 to 12 months of the follow-up period. One patient was lost to follow-up and one patient showed local recurrence within 4 months. In this patient the tumor was more extensive involving the limbal conjunctiva and the cornea. The early side effects of beta radiation reported by all five patients were temporary local irritation of the eyes with additional mild chemosis in four patients. None of the other three potentially cured patients showed any long-term adverse reactions. There were no incidence of late radiation induced complications such as corneal ulcerations, damage to cornea, eye pain, cataract or any other serious effects in these patients within the follow-up period. In conclusion, beta irradiation is an effective post-surgical therapy for local control of superficial conjunctival squamous cell carcinoma. The very low and minimum side -effects of Sr-90 irradiation is an advantage, which makes it a good alternative to external beam radiation, which has serious side effects.

A retrospective analysis of the effectiveness of Sr-90 therapy in post-operative management of pterygium. Between June 1999 and May 2001 a total of 70 patients received beta radiation for treatment of pterygium at the Institute of Nuclear Medicine &

Ultrasound, Dhaka. The patients were referred by the eye surgeons soon after excision of the lesion for beta radiation to the affected area. Hand held Sr-90 contact applicator from Amersham International was used to deliver a total dose of 2500 cGy radiation to the sclera surface in five fractions. Care was taken to anesthetize the eye(s) before each application. The patients were then followed up at one week, one month, six months and one-year interval after beta irradiation. The age range of the patients suffering from primary pterygium was 18 to 40 years. All patients underwent surgical excision with bare sclera technique. Of the patients treated 42 patients were completely lost to follow up, while 28 patients were followed up at different periods for up to 12 months. In these patients the local control rate of pterygium after irradiation was 94.6% after 12 months. Recurrence of the pterygium occurred in 5.4% of cases who were given a second course of strontium therapy. Follow- up after six months showed these patients to remain free of the disease. Associated complications were mild and included conjunctivitis. There was improvement of visual acuity in 21 patients with no evidence of cataract or ulceration noted in any of 28 patients during the 12-month follow-up period. In conclusion, beta irradiation with Sr-90 after surgical excision of pterygium was found to be a safe a nd cost- effective means of controlling the recurrence rate of pterygium.

To see the incidence of second cancers in patients with well differentiated thyroid carcinoma after being treated with radioiodine. Medical records of 814 (417males, 397females) patients with differentiated thyroid cancer treated at Institute of Nuclear Medicine & Ultrasound, Dhaka were reviewed. The purpose was to investigate the incidence of second cancer in these patients after radioiodine therapy. The age range of the patient population treated with radioiodine was 9 to 69 years. Doses of radioiodine given were in the range of 30 to 100mCi for ablation and 150 to 250mCi for treatment of metastasis. The median follow-up period was 93.7± 15months. Eleven (1.35 %) of the 814 patients developed a second malignancy. Two patients (0.25%) developed chronic myelogenous leukemia within a latency period of 5years and after receiving a cumulative dose of 600- 670mCi. The over all incidence of second malignancy in the form of solid tumors was 1.10%. Of the nine patients with solid tumors, there were two patients with renal cell carcinoma, three patients with parotid gland tumor, one patient with pancreatic cancer, one with adenocarcinoma of the stomach, one with carcinoid tumor and one with small cell carcinoma of the lungs. The mean latency period for development of these tumors was 6.92 ± 3.934 years and the mean cumulative dose received by all these patients was 537.25± 120.55 mCi. Follow-up of a fairly large cohort of patients treated with radioiodine showed a low incidence of second neoplasm. No relation was observed between the cumulative dose received and the development of a second malignancy. Thyroid carcinoma is a polygenic disease, which may be associated with other malignancies. Common environmental or genetic factors as well as long-term carcinogenic effects of radioiodine therapy should be considered.

014-BGDSecond Malignancies Following The Treatment of Differentiated Thyroid Carcinoma With RadioiodineYasmin, S, Nisa L, Haque FS, Begum R. Institute of Nuclear Medicine & Ultrasound, Dhaka Center for Nuclear Medicine & Ultrasound, Mitford Hospital, Dhaka.

S-17



015-BRAUse of Samarium 153 Hydroxyapatite for intra-articular therapyAnselmi OE

016-BULTc-99m MIBI and I-131 scintigraphy in the follow-up of differentiated thyroid carcinoma (DTC) patients after surgerySergieva S, Hadjieva T, Botev V, Dudov A. Sofia Cancer Center, UH “Queen Joanna”, Sofia, Bulgaria

017-CHIPeptide Receptor Radionuclide Therapy With Y-90-Dotatoc (somatostatin Analog) in Neuroendocrine Tumours: The Chilean Experience

1-2 1 1 3 2 1Amaral H , Pruzzo R , Morales B , Gil C , Coudeu I , Rojas A , 1-2 1-2 1-2 1 2Majlis A , Kleinman S , Vogel C , Rossi R , de la Fuente H ,

2 1 4 4Reyes C , Varas M , Chinol M and Paganelli G1 2 3Clinica Alemana, Fundacion A. Lopez Perez, CGM Nuclear,

4Santiago (Chile) and European Institute of Oncology, Milan (Italy).

Abstract not received

MIBI scan has been reported to be a highly sensitive imaging technique for detection of differentiated thyroid carcinoma (DTC) metastases that have lost the capability to take up I-131. The purpose of the present study was to evaluate retrospectively the value of the Tc-99m MIBI scan and I-131 whole body scintigraphy using thyroglobulin (Tg) levels as a basis for comparison. Eighty four patients (63F/21M) with an age range of 17-74 yrs (mean age = 43.5 yr) of DTC (47 cases with papillary, 18 cases with follicular and 19 cases with mixed papillary-follicular ) were assessed. All of them had undergone total or near-total thyroidectomy and received radioiodine treatment for ablation of post surgical residual thyroid tissue. They were examined after L-thyroxin withdrawal over 4-5 weeks during the follow-up period. Planar and whole body images were acquired at 15 min and 180 min after i.v. administration of Tc-99m MIBI (555-740 MBq) and at 48 hours after p.o. administration of I-131 (111-185 MBq) on Toshiba GCA gamma camera. Serum Tg assays were performed to clarify the presence of residual recurrent malignancy. All scintigraphic findings were compared with US, CT or MRT data. I-131 scans were positive in 55 patients showing thyroid remnants in 31 cases, lymph node metastases in 24 cases (17 in the neck, 7 to neck/mediastinum), pulmonary metastases in 6 cases and bone lesions in 2 cases. In 18 patients I-131 scans were negative and Tg levels were undetectable, so patients were considered tumor-free. In 11 patients I-131 scans were negative while serum Tg levels were increased. These false negative results were observed predominantly in cases with less differentiated metastatic cells, especially after several courses of high-dose I-131 therapy. Tc-99m MIBI scans revealed the presence of lymph node and/or lung metastases (non-functioning metastases) in 9 of them, false negative results were obtained in 2 cases. Serum Tg was increased in all patients with local lymph node and distant metastases, visualized by I-131 or by Tc-99m MIBI, but also in 18 patients with thyroid remnants only. Considering I-131 scan as the most specific standard procedure we may conclude that the combined Tc-99m MIBI scintigraphy and serum Tg assay appear to be an alternate method for large dose I-131 scan for demonstrating the extent of the disease in cases with DTC and elevated Tg.

Most of neuroendocrine tumors (NT) and a few others have an over-expression of somatostatin receptors in their cellular surface allowing “in vivo” detection of both primary tumors and its metastasis by diagnostic scintigraphic images with Octreotide

111labeled with In. Patients with inoperable, residual or metastatic NE tumors have typically a poor response to conventional radiotherapy or chemotherapy. A new valid option for therapeutic purposes in such cases is the use of a similar peptide like DOTA-

90D-Phe-Tyr-Octreotide labeled with Yttrium-90 ( Y-DOTATOC). This radiopharmaceutical is a pure beta emitter with specific affinity for subtype 2 somatostatin receptors allowing a high radiation dose to cellular level in NT. With the strong collaboration of the European Institute of Oncology, Milan (Italy), we have successfully incorporated this therapy in Chile including both the local labeling of the radiopharmaceutical and the design of the clinical protocols. We have treated 23 patients, 11 men and 12 women (average 46.6 y.o. range 12-70), 22 with histologically confirmed residual or metastatic NT and 1 hepatoma. All of them had positive

111somatostatin receptors demonstrated by In-Octreotide scintigraphy. The primary tumor was pancreatic (10), intestinal (5), medullary thyroid carcinoma (2), thymus (1), bronchial (1) and unknown origin (3). All patients received renal protection with crystalline amino acids immediately before the

90radiopharmaceutical administration. The Y-DOTATOC, labeled 90at CGM Nuclear in Santiago with Y from MDS Nordion

(Canada) and peptides from Pichem (Austria), was administered intravenously in single doses between 25-240 mCi (maximum total individual dose of 537 mCi). The whole group received 66 single therapy doses. Until now 16 patients have received more than one dose, 2 doses in 6, 3 in 2, 4 in 2, 5 in 4, 6 in 1 and 7 in 1. Only this sub-group is considered for evaluation of treatment response. Radiochemical controls were done in minicolumns Sep-Pak C18 previously to the patient injections. Radiochemical control showed a labeling efficiency of the radiopharmaceutical higher than 99%. In 16 patients with more than one cycle there has been complete remission of the tumor activity in 1, significant partial remission in 10, partial remission in 3 with further relapse and progression in 2. The treatment was well tolerated in all the patients except in one in whom by causes not yet determined the “in vivo” biodistribution of DOTATOC was altered showing mainly bone marrow uptake (non-tumor) of 90Y presenting a severe but reversible hematological toxicity. This patient was considered non-treated since there was no selective tumor irradiation. The other patients showed mild reversible hematological toxicity. In a 36 y.o. female patient suffering a progressing pancreatic NT with multiple metastasis and severe bone marrow involvement presenting partial response and further relapse, a high rescue dose of 240 mCi was administered following a successful autologous stem cells transplantation. The patient is now asymptomatic with significant partial response.

90These preliminary data indicate that the treatment with Y-DOTATOC, now available in Chile, is a valuable therapeutic option for these type tumors that frequently do not respond to conventional treatments like chemotherapy or external radiotherapy. Peptide receptor therapy should be considered as first line treatment in well-differentiated NT.

S-18



018-COLRe-188 Lipiodol Therapy of Hepatocellular CarcinomaBernal P, Chau T, Erdenechimeg S, Kumar A, Srivastava D, Pusuwan P, Ang S, Barrenechea EA, Jeong JM, Onkhuudai P, Knapp FF, Sundram FX, Divgi C, Buscombe J, Dondi M, Padhy AK. (Based on the results of an International multi-centric study initiated by the IAEA)

Hepatocellular carcinoma (HCC) is a malignant epithelial tumour arising from parenchymatous liver cells. It is one of the world's most common malignancies, causing almost one million deaths annually. About 315,000 new cases of HCC are reported per year which constitutes 5.6% of all cancers among males and 2.7% of all cancers among females. Control strategies to prevent occurrence of HCC are sub-optimal; this is evident by the rising incidence of HCC even in developed nations like the USA, where the prevalence of the disease is one of the lowest in the world. Currently, patients with HCC have an extremely poor prognosis with a five year survival rate of less than 5% . However, morbidity and mortality in such patients are not determined by the presence of HCC alone, but are also influenced by the activity of the underlying liver disease, as well as the functional status of the liver. The stage of the tumor (size, number, vascular invasion, extra hepatic spread) has been consistently documented to be an important determinant of the natural course of the disease. These factors are major variables that influence various therapeutic strategies directed against this tumor in recent times. Therefore, therapy in HCC needs to be optimized depending upon the above mentioned influences on the final outcome of the disease.Various forms of therapy such as surgical resection, orthotopic liver transplantation (OLT), percutaneous injection to induce coagulative necrosis of the tumor using agents like ethanol, acetic acid, hot saline, microwave and laser have been considered as radical treatment of HCC, aiming at curing the disease. The understanding of pathology, pathogenesis, natural course and risk factors of HCC during the last three decades has resulted in the development of multiple therapeutic approaches with promising yet varying results. Most patients with hepatoma from the developing countries at the time of their presentation to the doctor fall into the intermediate/inoperable category , and for these, radionuclide methods to deliver high radiation doses to tumor must be considered. Uncontrolled studies using radioisotopes like I-131, Y-90, Ho-166, Re-186 conjugated to monoclonal antibodies, lipiodol or chemical compounds have shown promising results. However due to lack of prospectively designed randomised trials, their efficacy is yet to be optimally evaluated. There has also been reports (from one study only) on the usefulness of radionuclide therapy as an adjuvant treatment following resection of “curable” HCC. It has been shown that patients given a single administration of 1GBq. Of I-131 Lipiodol have significantly greater survival and less recurrence than those not treated. It is important that the results of this study be verified and confirmed by reproducing the results in another prospective trial. It may be noted that the disease is most prevalent in those communities with least resources for setting up clinical trials. Hence the role of the International Organizations like IAEA and WHO are extremely important in assisting them in setting up such trials and coordinating them. For nuclear medicine and the IAEA-WHO to develop a key role in the treatment of HCC, new methods must be evolved, tested and standardized in full random controlled trials.Currently the only commercially available radiopharmaceutical

for the treatment of liver cancer, I-131 Lipiodol, has been found to be prohibitively expensive, and it is virtually not practical to use this radiopharceutical on a routine basis in the poor and developing countries of the world. In the year 2001 the IAEA started a new coordinated research in order to identify and test a new cost-effective radiopharmaceutical for the treatment of liver cancer. With the help of scientists for Korea, Singapore and USA it has been possible to label Rhenium 188 with Lipiodol which has shown excellent concentration in the HCC when administered trans-arterially. Phase-1 study revealed that the right quantity of the radioconjugate can be delivered after 'scout' dose dosimetry studies have been done, to spare normal liver and lung from excess radiation dose. The phase-1 data showed that the treatment is safe with minimal side-effects, at a dose up to about 200 mCi of Re-188 lipiodol. The Phase-2 study in over 100 patients revealed excellent results. With a median follow-up time of 449 days, the results have demonstrated one-year survival rate of 56%, while at the time of the analysis (which was almost two years after treatment for some patients) the survival rate was found to be 40%; which is remarkable keeping in view the types of patients recruited, most of who were end-stage disease.

For the treatment of differentiated thyroid cancer, surgery, radioiodide therapy, and thyrotropin-suppressive thyroxine application represent established therapeutic measures of proven efficiency, affording a good prognosis for this disease. However, in up to 30% of the cases, de-differentiation is observed, giving rise to tumours that are refractory to conventional treatment. Experimental data shows strong evidence that differentiated functions of iodine metabolism can be re-induced by retinoic acids (RA). The aim of our study was to assess the effects of retinoic acid therapy in patients with extensive thyroid tumor involvement, which lost radioiodine uptake ability. Twenty-five patients who received retinoic acid therapy between Feb. 1999 to Dec. 2004 were reviewed retrospectively. There were 15 males and 10 females with a mean age of 52.5 years (16-71 years). Most of them underwent total or near total thyroidectomy before I-131treatment. Twenty-one patients were papillary carcinoma and four were follicular carcinoma. Twenty-two patients had lung metastasis and three had bone metastasis. Thyroid hormone medications were withdrawn for two weeks in case of triiodothyronine (T3) and five weeks in case of thyroxine (T4). For treatment of bone metastases, an amount of 7.4 GBq (200mCi) of I-131 was given every six months. For treatment of pulmonary metastases an amount of 5.55-7.4 GBq (150-200mCi) was given every six months. In 25 patients with advanced thyroid cancer, whose cancer foci did not concentrate radioiodine, retinoic acid was given for 6 weeks before radioiodine treatment, followed by I-131 treatment. All patients had I-131 scans and thyroglobulin measurements 7 days after administration of I-131. X-ray, bone scan, and ultrasound of the neck were done one month after administration of I-131. One patient received RA therapy four times and two patients received RA twice. In the post-therapy radioiodine scans, radioiodine uptake was noted in 9 patients with lung metastases and in 2 patients with bone metastases. On the whole, in 44% (11/25) of patients re-induction of radioiodine

019-CPRRetinoic Acid in Patients with Radioiodine Non-Responsive Differentiated Thyroid Carcinoma.Zheng R, Zhang W, Li J, Chen S. Department of Nuclear Medicine, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing 100021, P. R. China

S-19



uptake was observed. Levels of thyroglobulin concentration before and after RA therapy did not differ significantly (P>0.05). In our study, all patients completed the treatment and the most frequent side effects were fatigue. Dry skin, mouth and lips occurred in 35% of patients. Most side effects were well tolerated by the patients and reversible following cessation of RA therapy. We conclude that retinoic acid can induce radioiodine uptake and the side effects are well tolerated. However, prospective studies in larger groups of patients are necessary to prove its clinical utility in routine practice.

020-CPRStudy of the Therapeutic Dose and the Clinical Effect on Graves’ Disease With I-131 TreatmentY. Dang. Imaging Diagnostic Center of Nanfang Hospital, Southern Medical University, Guangzhou, China

Graves’ disease is being treated with I-131 for more than 40 years in China. Previously the dose of I-131 used to be calculated using the “Quimby” formula. We have now observed that the dose of I-131 administered to patients is now lower in recent years than the early years. The radioactive iodine uptake by the thyroid gland has also changed significantly over a period of time. In this paper we intend to explore these reasons and to research the relationship between the dose and the effect as well as the main cause of the incidence of the hypothyroidism. The parameters in “Quimby” formula including I-131 uptake, effective half-life and thyroid weight were analyzed and compared with each year data from 1961 to 1988 and subjected to multiple regression analysis to determine the influence on the calculation of dose in 4465 patients. The therapeutic effects were compared with the data of the clinical follow-up of patients between 1961-1973 and 1978-1988 in 748 patients. The factors which might lead to the hypothyroidism were investigated with the non-condition logistic regression. The I-131 uptake was repeatedly measured within one week in 100 patients to identify the changing pattern of the I-131 uptake and its influence on the administered therapeutic dose. We observed an increase in the value of I-131 uptake. The value of I-131 uptake showed an increase after 1977, as well as a prolongation of effective half-life after 1973. The main reason for these changes being a replacement of the equipment in 1977 (G-M counter tube was replaced by scintillation counter), and the other reason being salt iodization in China in 1973. These two factors resulted in a significant reduction in the administered dose of I-131 during the period 1974-1988 as compared to the previous period 1961-1973; the mean administered doses being 168.35MBq and 330.33MBq respectively. The result of multiple regression analyses suggested that the thyroid weight and the effective half-life were the most important factors to influence on the dose calculation. The therapeutic effects demonstrated that it was significantly different between 1961-1973 and 1978-1988. The incidence of hypothyroidism in 1961-1973 was obviously higher (58.58%) than in 1978-1988(19.01%). The non-condition logistic regression of the factors which lead to the hypothyroidism were analysed, which showed that the individual sensitivity and the higher administered doses were the main causes of hypothyroidism. The data also showed that the results were highly satisfactory when the administered doses were within 111-222MBq or 2.59-4.07MBq/g. The coefficients of variation (CV) of the mean value of the two peak I-131 uptake values determined within one week in 100 patients was12.78. The biggest CV was 61.42%. There were 41% patients with CV=10%. The absolute difference mean value of the two peak I-131 uptake rate and

calculating dose was 11.08%?44.03 MBq. The biggest different value was 44.26% and 446.59 MBq, respectively. To sum up, the dose and the therapeutic effect had a significant difference in the different period of the years although the therapeutic method and the calculating formula was the same. Therefore, the scientific and feasible function of the “Quimby” formula should be considered deeply. Moreover, the uptake rate of I-131 was changed significantly in a short period. In order to solve these problems, on the basis of our experience, according to the individual sensitivity and the exceeding dose were the main causes of the incidence of the hypothyroidism, we put forward to simplify the therapeutic method. We suggested to choose the thyroid weight as the only factor-thyroid weight times a fixed coefficient, to take into consideration the patient’s clinical condition and to choose the dose within the range of 111-222 MBq or 2.59-4.07MBq/g as a suitable optimal dose for therapy.

021-CZROur Experience With Radioiodine Therapy of Thyroid Functional Autonomies Otakar Kraft. Department of Nuclear Medicine, University Hospital, Ostrava-Poruba, Czech Republic

In this paper the author presents his experience with radioiodine therapy of thyroid functional autonomies. The objectives of this study were to establish the efficacy and determine the adverse effects of radioiodine therapy of patients with thyroid functional autonomies. The main pathologic attribute of thyroid functional autonomies is the loss of regulation in the axis of hypothalamus-hypophysis-thyroid. The main cause of functional autonomy of the thyroid is iodine deficiency. Over a period of 30 years (1974-2004) 799 patients (age from 33 to 86 years; average age 58.7 years; the female: male ration was 7.4:1) with unifocal functional autonomy (UFA), multifocal functional autonomy (MFA) and disseminated functional autonomy (DFA) received at least one treatment of radioiodine. For diagnostics and the evaluation of radioiodine therapeutic effect of functional autonomies a thyroid scintigraphy is the basic and necessary procedure. In some patients a common scintigraphy with special imaging modulation, in some patients a scintigraphy after suppression or stimulation by means of thyroid hormones or TSH were done. We have also performed a thyroid ultrasonography, an assessment of a serum level of a total and free thyroxine, total triiodothyronine, TSH, radioiodine accumulation test, estimation of radioiodine effective half-life, in some patients TRH-TSH test. The follow-up examinations were done in all patients after 4-6 months, another examination after one year in 545 patients and after two years in 254 patients. One therapeutic dose received 733 patients (91.74%) and it was sufficient for an elimination of functional autonomies. Some patients were re-treated if there was the evidence of small or no treatment effect and no elimination of functional autonomies. Two radioiodine treatments received 62 patients (7.76%) and three treatments 4 patients (0.5%). We advocate individual pre-therapeutic dosimetry to determine the activity necessary to achieve a targeted radiation dose in autonomously functioning tissue. The radioiodine amount administered was based on the volume of thyroid or the nodule, 24-hours radioiodine accumulation, the effective half-life of radioiodine, the absorbed dose of 500 Gy per gram of the nodule (UFA) or 300 Gy per gram of the whole thyroid (in patients with MFA and DFA). Before radioiodine therapy an average serum levels of total thyroxine was 164.6 nmol/l, of free thyroxine 20.8 pmol/l and

S-20



triiodothyronine 3.2 nmol/l, in all patients TSH was suppressed. Before therapy patient's complaints were cardiovascular in 88% of patients (tachycardia, irregular pulse, palpitation), neurological (nerves, agitation) in 72% of patients, hypermetabolic (loss of weight, intolerance of warm, perspiration) in 68% of patients and local (feeling of neck compression, swallow difficulties) in 30% of patients.After therapy the average serum levels of total thyroxine was 108.8 nmol/l, free thyroxine 12.5 pmol/l and triiodothyronine 2.0 nmol/l and improvement of symptoms in 91%, without improvement in 8.7% and worsening in 0.3% of patients. The suppression of TSH disappeared in 607 of treated patients (76%). A volume reduction of thyroid of 38% was achieved in any type of functional autonomy after radioiodine treatment. Side effects were minimal and in some patients presented as a transient neck pressure or pain and neck swelling as a manifestation of post radiation thyroiditis. Post radiation hypothyroidism was diagnosed in 36 patients (4.5%). The results of this study show that the radioiodine therapy of the thyroid functional autonomies is safe, with low incidence of adverse effects. It is effective and for patients non-demanding.

In this paper the authors present their experience with radiosynoviorthesis (RSO) and re-radiosynoviorthesis (re-RSO) of knees. The objectives of this study were to compare treatment results between first RSO and re-RSO.Before RSO an ultrasonography (USG), an X-ray, a three-phase bone scintigraphy (TPBS). The treatment effect (TE) can be expected if a synovitis is proved by these examinations.To knees we inject 200 MBq of the yttrium citrate. TE is evaluated by the clinical examination, USG and TPBS. If the effect of RSO is not satisfying, RSO can be repeated no sooner than 6 months later. Among our patients we have high percentage of re-RSO. A rate between single RSO and re-RSO was 11:8. From 1986 to December 2004 we treated 1267 knees with Yttrium Citrate 37.9% patients had gonarthrosis, 26.1% chronic synovitis, 20.3% revmatoid arthritis, 4.6% relapsing fluid, 3.9% psoriatic arthropathy, 3.3% ankylozing spondylarthritis and 1.3% hemophilic arthropathy.The evaluation of TE by patients in 294 RSO (170 patients with single RSO and 124 pts with re-RSO an influence on a pain and a fluid formation after single RSO: 10.9% no influence, 42.2% substantial and long-term effect, 46.9% partial TE and after re-RSO: 8.2% no influence, 36.6% the substantial and long-term TE, 55,2% the partial TE. The best results evaluated by patients were in patients with the revmatoid arthritis and heamophilia. Worst results were in osteoarthritis in case of considerable radiological changes. Clinical follow up of 110 pts with single RSO and 70 pts with re-RSO: after single RSO: after 6 months in 77% swelling and a filling reduction and in 86% pain reduction, after 1 year in 53% the swelling and the filling reduction and in 62% the pain reduction, after 2 yrs in 28% the swelling and the filling reduction and in 48% the pain reduction; after re-RSO: after 6 months in 62% the swelling and the filling reduction and in 75% the pain reduction,

022-CZROur Experience With Radiosynoviorthesis and Re-Radiosynoviorthesis of Knees1 2Otakar Kraft, Richard Kaspsrek1 2Department of Nuclear Medicine and Department of Orthopaedics, University Hospital, Ostrava-Poruba, Czech Republic

after 1 year in 43% the swelling and the filling reduction and in 61% the pain reduction, after 2 yrs in 35% the swelling and the filling reduction and in 51% the pain reduction. After RSO we have observed a significant reduction of blood pool activity and synovial swelling with further improvement in the following months. There is a strong correlation between the reduction of blood pool activity (apparent on TPBS), synovial swelling (apparent on USG) and improvement of pain.Ultrasonography finding: Single RSO: before therapy: marked filling and synovial reaction with villus; after 6 months, 1 year and 2 years: without treatment effect - the same ultrasonographic finding; partial effect - the reduction of the filling, synovial villus and synovitis have not diffuse character; substantial effect minimal filling without synovial reaction. Re-RSO: before therapy: marked filling and synovial reaction with villus; after 6 months, 1 year and 2 years: without treatment effect - similar ultrasonographic finding as before treatment with some ligamentous reaction; partial effect - the reduction of the filling, synovial villus and the synovitis have not diffuse character with synovial ligamentous reaction; substantial effect - without filling and minimal synovial reaction with sporadic occurrence of synovial villus, synovial ligamentous reaction. Radiographic finding:Before therapy it depends on the primary diagnosis. After single RSO: without therapeutic effect - after 6 months: it does not change or it impairs; after 1 and 2 years: it impairs; partial treatment effect: after 6 months: it does not change, after 1 and 2 years: it does not change or it can impair; substantial efect: after 6 month, 1 and 2 years: radiographic finding does not impair, it does not change. After re-RSO: entirely the same radiographic finding as after single RSO. TPBS: The finding before single RSO and re-RSO: positive the first two phases of TPBS.After single RSO: without therapeutic effect - after 6 months, 1 and 2 years: it does not change with higher bood pool, partial treatment effect: after 6 months, 1 and 2 years: blood pool can be higher but not so much as before treatment; substantial efect: after 6 month, 1 and 2 years: normalization of blood pool. After re-RSO: entirely the same blood-pool finding as after single RSO. We have observed side effects of the therapy in 5% patients in the form of a radiation synovitis which has subsided after 2 or 3 weeks during combined symptomatic therapy with antirevmatics, orthesis and subsequent rehabilitation.RSO is effective, simple and for patients the convenient treatment procedure with a low occurrence of undesirable effects. Repeated RSO were as effective as single RSO, and its repeated use does not decrease the expected TE.

In this paper we present our experience with the cooperation in the treatment of Slovak patients with differentiated thyroid cancers in Slovak and Czech hospitals. The treatment capacities in the

023-CZRInternational Cooperation in the Treatment of Patients with Differentiated Thyroid Cancers1 2Otakar Kraft, Ivan Reznak1Department of Nuclear Medicine, University Hospital, Ostrava-Poruba, Czech Republic2Department of Nuclear Medicine, University Hospital, Martin, Slovak Republic

S-21



Slovak nuclear medicine departments are not sufficient for radioiodine therapy of patients with differentiated thyroid cancers and that is why these patients are sent for this therapy to Czech nuclear medicine departments. The objectives of this study were to demonstrate the way of this cooperation and the results of therapy. We concentrated on the collaboration between the Department of Nuclear Medicine in Martin in the Slovak Republic and the Department of Nuclear Medicine in Ostrava, the Czech Republic. From 1991 to 2005 hundreds patients with differentiated thyroid cancers (follicular, papillary) underwent a complex therapy. In Slovak hospitals they were diagnosed and operated on for the cancer (near-total thyroidectomy and removal of lymph node metastases). Then they were sent to the Department of Nuclear Medicine in Ostrava in the Czech Republic. In this department a radioiodine ablation of thyroid remnants by means of the treatment dose of radioiodine of a standard activity of 3,7 GBq was performed and then a suppression and substitution therapy of thyroid hormones were started. After 3-6 months some patients were examined by means of the diagnostic whole body

131scintigraphy after application of 300 MBq I. Some patients were 131treated by means of a standard activity of 7,4 GBq I and after 5

days the whole body scintigraphy (WBS) was performed. In these both groups of patients the diagnostic or therapeutic radioiodine application were done after withdrawal of thyroid hormone treatment. If thyroglobulin levels were low and WBSs were negative, patients were followed up in the Department of Nuclear Medicine in Martin. Patients with radioiodine accumulated metastases were again treated with radioiodine in Ostrava. If indicated, the external radiation therapy targeted on the neck and upper mediastinum was performed in the Slovak Republic, in University Hospital in Martin. Newly formed lymph nodes metastases were surgically treated in Slovakia, too. In this paper we analyze the treatment results in various groups in men, in women, in patients with follicular cancers, in patients with papillary cancers, in younger and older patients. We also present some interesting case reports. Generally we have very good treatment results with very low five years mortality. Also economically our partnership is cost effective. Our collaboration successfully continues also after entrance of the Slovak Republic and the Czech Republic to the European Union in 2004. The results of this multi-center study show that international Czech and Slovak cooperation in the complex therapy of patients with differentiated thyroid cancers is successful, with high efficacy. The treatment results are very good.

In this paper we present experience in Dominican Republic on Radiopharmaceutical Therapy. In our country, there are 8 Center with Nuclear Medicine Department. Only, 7 centers are working with Radiopharmaceutical Therapy. Radioiodine treatment with I-131 in Thyroid diseases(Thyroid Cancer and Hypertyroidism). This is only Nuclear Medicine therapy available in Dominican Republic. The objectives of this paper are to analyze and assess the difficulties and facilities for the development of Radiopharmaceutical Therapy in Dominican Republic. We made surveys with the help of Nuclear Medicine Physicians of different Nuclear Medicine departments. 8 Nuclear Physicians accepted the

024-DOMRadiopharmaceutical Therapy in Dominican Republic. Present and FutureJohny Osvaldo de los Santos, M.D.Department of Nuclear Medicine, Instituto Oncologico Regional Cibao. Santiago Dominican Republic.

interview. Two of these Nuclear Medicine Centers are Department of a Cancer Center and they have many patients for therapies. In the majority opinion of Physicians, Cost of Radiopharmaceuticals is principal problem to use Therapy in Dominican Republic. In addition the following problems were identified: Lack of awareness about new therapy in Nuclear Medicine among Physicians of other specialties, lack of adequate training in the current trends of radionuclide therapy and finally lack of basic infrastructure, equipment and finances to buy radiopharmaceuticals and introduce radionuclide therapy. For this reason, Nuclear Medicine Centers prefer to work with only I-131 Therapy and they do not have new programs to start other therapies. In the near future, our deparment of Nuclear Medicine will work with I-131, pain palliation, treatment of metastatic disease and Treatment of benign diseases. We have interest in offering other therapies in the department and we hope that other departments with more resources, have the same interest, to enhance practice of radionuclide therapy in our Country.

025-EGYOsteosarcoma Target Therapy With Stem Cell Transplant: A Case ReviewFawzy A.Nuclear Medicine unit, Faculty of Medicine, Cairo University, Egypt.

Radioisotopes with medium-energy beta emission and half life of a few days are attractive option for systemic delivery of targeted irradiation. Samarium-153 ethylene diamine tetra-ethylene phosphonale (153Sm-EDTMP), a bone-seeking radio-pharmaceutical, provides therapeutic irradiation to osteoblastic osseous lesion. The usual dose of Sm-153 in metastatic disease is 1mCi/Kg (37MBq/Kg) and the dose limiting toxicity is thrombocytopenia. As local radiotherapy has only a limited therapeutic role in the treatment of osteosarcoma, and some types of the tumour portray an unpredictable response to chemotherapy. High dose Sm-153 (30mCi/Kg) was proposed for the target management of recurrent osteosarcoma, this was followed by stem cell transplant (peripheral-blood progenitor, PBPCs).A female child, 10 years old, with polyostotic osteosarcoma with local recurrence in the right hipbone was chosen for therapy. She had left knee prosthesis, right lower limb disarticulation, and was given chemotherapy in multiple regions. She was subjected to MDP bone scan showing active uptake in an expanding bone lesion in the right hip bone, and was also subjected to MIBI scan, which showed negative uptake.She received 30mCi/Kg Sm-153 (660mCi in total dose), with no major events occurring in the post-injection period. After 10 days the patient went into pancytopenia, which necessitated haematological support. By day 14, there was minimal radiation in the whole body image and the child received her bone marrow transplant.There was marked improvement in the tumour size after 6 weeks of therapy, with improvement in the alkaline phosphatase level (from 1350Iu, before treatment to 350 post treatment). This was confirmed by serial MDP bone scan. High dose Sm-153 with stem cell transplant is considered view a promising method in the management of osteosarcoma.

S-22



0

In Estonia first radiosynovectomy (RSE) was carried out in 2001 at Tallinn Central Hospital, which has remained the only institution in North Estonia performing these procedures. Purpose of this study was to analyze the results and the clinical experience gained during the period of September 2001 January 2005. We performed RSE in 10 knee joints of 7 patients. Our patient population consisted of 3 males and 4 females (mean age 34, range 16-48). There were 6 patients with rheumatoid arthritis (RA) and chronic synovitis and 1 patient with haemophilia (HE) who had one episode of hemarthrosis eight month prior to RSE. In RA the duration of the disease was ranging from 2 month to 20 years. All RA patients were resistant to anti-inflammatory drugs, immunosupressants and intraarticular steroid therapy. Prior to RSE, conventional rheumatologic evaluation and MRI scan were carried out, revealing the thickness of synovia of 2-5 mm, and minimal or no cartilage damage. In our HE patient chronic hypertrophic synovitis associated with haemarthrosis did not respond to haematological treatment: replacement of the missing clotting factor, intermittent steroids, immobilization, physical therapy. According to MRI, the thickness of synovia was patchy, 5-26 mm, the cartilage damage was absent. For RSE, intra-articular injection of radiocolloid was carried out in aseptic conditions and under local anesthesia. Treated joints were immobilized for 2 days. In 5 out of 6 RA patients the injection was performed once, in one RA patient four times. In order to minimize local inflammation and lymphatic clearance glucocorticoids were administered together with radioisotope agents. In three patients (2 with RA and 1 with HE) 27 mCi of 166-Ho-FHMA was injected, and in remaining four patients with RA - 4-6 mCi of 90-Y radiocolloid was used. All joints with Ho-FHMA were checked for radiocolloid leakage by subsequent gamma camera imaging. Treatment response was evaluated from 2 to 6 month after RSE by presence of tenderness and swelling of treated joint, functional status, and using visual analogue pain scale (0-10 point gradation). In 6 cases (5 RA and 1 HE) repeated MRI was performed after RSE. Improvement in local clinical signs was noted in 6 RA cases out of 9 (67%), insufficient improvement - in 3 (33%). In two RA patients (5 therapy cases) with follow-up MRI, decrease of synovia up to 0,5-2 mm was observed. In one RA patient RSE was performed four times, providing relief in clinical

stsigns after every treatment, and decrease of synovia after the 1 ndand 2 injection. In HE we did not observe any change in synovia,

but during the follow-up period of more than 3 years no repeated haemarthrosis has occurred. We did not observe any general or local symptoms of radiation sickness in our patients. In conclusion, RSE is a safe and effective tool for the management of synovitis in RA and HE patients.

Neuroblastomas (NB) belong to a group of neuroendocrine

26-ESTRadiosynovectomy: First Results in Estonia

Nazarenko S, SamarinaG, Poksi ANorth Estonia Medical Centre, Tallinn, Estonia; Department of Nuclear Medicine, East Tallinn Central Hospital, Estonia

027-ESTOur First Experience in the Application of I-131 MIBG in a Patient with Neuroblastoma (A case report)Samarina G, Poksi ADepartment of Nuclear Medicine, East Tallinn Central Hospital, Estonia

tumors that are thought to arise from cells in the neural crest from the pelvis to neck, produce high levels of the urinary

catecholamines vanillylmandelic acid (VMA) or homovanillic acid (HVA) in more than 90% of cases, and often metastasize to

bones, bone marrow (BM), lymph nodes, and the liver.I-123 MIBG andI -131 MIBG a re c l in i ca l ly impor t an t radiopharmaceuticals, which are routinely used for diagnostic imaging and treatment of NB. 90% percent of NB takes up the MIBG. If, however, the MIBG cannot successfully attach to a patient's tumor, it cannot be used to find or treat it. A 20-month-old girl presented with a 6-month history of a rapidly growing tumor mass 3.5 cm in diameter in the left orbital region. The first CT scan revealed a soft tissue tumor 22 x 28 mm, extending from the inferolateral wall of the left orbit and destroying the surrounding bone (os zygomaticus). CT scans of the chest and abdomen were negative. Histopathology showed high malignancy (G3) of NB (immunohistochemical reactions: NSE positive, CgA positive, SY positive, Ki-67 70% of tumor cells positive). First BM histological examination revealed no pathological findings. Urinary VMA and HVA levels were within the normal range. Tc-99m MDP scans showed increased uptake of radiopharmaceutical in the bones around the left orbital region but no evidence of

123skeletal metastases. I-MIBG studies revealed a hypermetabolic focus in the left orbital region, concordance with the CT and bone scans. The child was treated with preoperative chemotherapy, but without any results: the CT-scan performed four months later showed that the tumor had grown to 45 x 37 x 40 mm. The clinical test demonstrated the progress of the disease and the tumor at that stage was inoperable. Clinicians decided to change the chemotherapy regimen and a CT study carried out three months later showed that the tumor had decreased to 26 x 10 x 30 mm. The patient was operated on whereby the tumor was partially resected from the left orbital region. A MRT scan performed two months later showed progression of tumor mass to the orbit (50 x 40 x 30 mm) with destruction of the maxillary sinus and metastases to BM in vertebrae and femoral bones. A subsequent BM biopsy demonstrated evidence of high malignancy of the tumor metastases. Repeated Tc-99m MDP bone scans were not positive for bone metastases. This year the patient had different combinations of chemotherapy constantly, but without any clinical success. At that stage a clinician of the Pediatric Oncology Department decided to perform I-131 MIBG therapy. The child's parents received information about the procedure and specific instructions concerning radiation safety precautions. In order to minimize thyroidal uptake of free iodide in the child and her father, they were given 200 mg of oral potassium iodide per day, which was started 48 hours before I-131 MIBG administration and continued up to 10 days after the therapy. The administration of the 162 mCi I-131 MIBG was performed during 2.5 hours with a radiation safety system, the patient being under supervision in an isolated and monitored hospital room. Side effects, such as mild nausea and vomiting, were observed immediately after the administration. During the therapies the child watched TV and videos, drew pictures and played with her games or toys. Radiation dosimetry was performed daily. After the I-131 therapy scan (the whole body and SPECT of the head and neck) we verified the presence of multiple sites of the tumor in the head (the left and right orbital region and the left parieto-occipital region) and bone marrow infiltration in the left arm and both lower

thlimbs. The patient went home on the 8 day after the injection of I-131 MIBG. During the first two weeks the patient's clinical condition was stable. During the next two weeks the clinical test showed rapid progression of the tumor in the left orbital region (it

S-23



had grown app. 2-3 times) but also tumor mass development in the right orbital region. Mild BM depression, such as leucocytopenia and thrombocytopenia, was verified. After a 4-week interval the I-131 MIBG therapy was repeated at the same dose level. The second therapy scan revealed that the primary tumor in the head had grown considerably and BM metastases had spread further - the first therapy had had no effect. In this case I-131 MIBG treatment failed to produce the desired result due the rapid progression of NB. The patient's clinical condition kept deteriorating after the second MIBG therapy and a few months

later the patient died. In conclusion, an accurate preoperativediagnosis of NB with I-131 MIBG is of crucial importance in

choosing the appropriate strategyfor the management of this kind of tumor. Our patient had progressive and intensely pretreated

stage IV disease. MIBG therapies were only performed after the other treatment modalities had failed. We do not have any experience with MIBG therapy in earlier stages of NB, but we believe that this treatment would be more helpful in patients with slower NB tumor progression.

Bone metastases are a frequent complication of cancer, occurring in up 70% of patients suffering from advanced breast or prostate cancer and often present with severe bone pain. In this purpose the radionuclide therapy is a useful option for cancer patients.

89 32 153Different radionuclides are described, such as Sr, P, Sm-186 131 90 188EDTMP, Re-HEDP, I-BDP3, Y, 117mSn-DTPA, Re-

188HEDP and Re-DMSA. The most experiences are available for 89Sr. An indication for the treatment are patients with osteoblastic metastases, bone pain, sufficient bone marrow function and at least of three bone metastases visualized in bone scan. A bisphosphonate therapy, a chemotherapy with lower bone marrow toxicity or a local field external beam radiotherapy represent no contraindications, especially because the reported synergistic effects to the systemic radionuclide therapy (1,2).In 33 treated patients (breast and prostate cancer) we investigated

188the effect of Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function. There were an improvement on the Karnofsky performance scale from 74 7% to 85 9% 12 weeks after therapy (p= 0.001). The pain score showed a

rd thmaximum decrease from 44 ± 18% to 27 ± 20% in the 3 to the 8 week after therapy (p = 0.009) and 76% had a pain relief (20% were pain free). The maximal differences between the values of platelets and leukocytes before and after therapy were not statistically significant (p= 0.021 and p= 0.094) (3). In 105

89 investigated patients treated with different radionuclides ( Sr , 153 186 188 89Sm-EDTMP, Re-HEDP, Re-HEDP and Sr in combination with chemotherapy) no different therapeutic efficacy of the

188treatments were observed (4), (5). In dose calculation of Re-HEDP a radiation dose of 3.83 ± 2.01 mGy/MBq (12.6 Gy for 3300 MBq) for bone metastases and 0.61 ± 0.21 mGy/MBq (2 Gy for 3300 MBq) were found. With the introducing of radionuclide treatments with chemotherapy and repeated treatments (1), (6), the calculation of bone marrow radiation-absorbed dose is more significant. But the dose calculation by MIRDOSE based on the hypothesis of a homogeneous distribution of the

028-GERTherapeutic Efficacy and Dosimetric Aspects of Rhenium-188-HEDP in Bone Pain PalliationKnut LiepeDepartment of Nuclear Medicine, University Hospital Dresden, Germany

radiopharmaceutical in the bone metastases and a 50% uptake in the cortical and trabecular bone. For calculation of the uptake animals studies were developed to induce osteoblastic bone metastases by intra-ossär administration of prostate cancer cells. In autoradiographic studies (BAS 500, Fuji; resolution of 0.5 µm)

188bone metastases and skeleton were investigated after Re-HEDP. In the bone metastases a tumour to muscle ratio (T/M) of 48 ± 7 and a tumour to non-tumour ratio (T/NT) of 9.7 ± 1.5 (7.5 to 11.7) was found. The distribution in the metastases was inhomogeneous with a minimal T/NT of 7.0 ± 1.0 (4.9 to 8.5) and a maximal T/NT of 17.4 ± 2.7 (11.6 to 22.6). The ratio between the trabecular and cortical bone in non-tumour bone was 68.6 ± 7.2% to 31.4 ± 7.2 %. The inhomogeneous distribution could favour high beta energy radionuclides for a more homogeneous dose distribution in bone metastases. The MIRDOSE calculation underestimates the bone marrow dose; the uptake in the trabecular bone is higher than in the cortical part. The higher uptake in the trabecular bone decreases the hypothetic dose reducing effect of low beta energy radionuclides to the bone marrow.

References1. Tu SM, Millikan RE, Mengistu B, et al. Bone-targeted therapy

for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet 2001;357:336-41.

2. Soerdjbalie-Maikoe V, Pelger RC, Lycklama a Nijeholt GA, et al. Strontium-89 (Metastron) and the bisphosphonate olpadronate reduce the incidence of spinal cord compression in patients with hormone-refractory prostate cancer metastatic to the skeleton. Eur J Nucl Med Mol Imaging 2002; 29:494-8.

3. Liepe K, Kropp J, Runge R, Kotzerke J. Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases. Br J Cancer 2003; 89:625-629.

4. Liepe K, Franke WG, Kropp J, Koch R, Runge R, Hliscs R. [Comparison of rhenium-188, rhenium-186-HEDP and strontium-89 in palliation of painful bone metastases]. Nuklearmedizin 2000; 39:146-51.

5. Liepe K, Runge R, Kotzerke J. The benefit of bone-seeking radiopharmaceuticals in the treatment of metastatic bone pain. J Cancer Res Clin Oncol 2005; 131:60-6

6. 1. Tu SM, Millikan RE, Mengistu B, et al. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet 2001;357:336-41.

7. 2. Soerdjbalie-Maikoe V, Pelger RC, Lycklama a Nijeholt GA, et al. Strontium-89 (Metastron) and the bisphosphonate olpadronate reduce the incidence of spinal cord compression in patients with hormone-refractory prostate cancer metastatic to the skeleton. Eur J Nucl Med Mol Imaging 2002;29:494-8.

8. 3. Liepe K, Kropp J, Runge R, Kotzerke J. Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases. Br J Cancer 2003;89:625-629.

9. 4. Liepe K, Franke WG, Kropp J, Koch R, Runge R, Hliscs R. [Comparison of rhenium-188, rhenium-186-HEDP and strontium-89 in palliation of painful bone metastases]. Nuklearmedizin 2000;39:146-51.

10. 5. Liepe K, Runge R, Kotzerke J. The benefit of bone-seeking radiopharmaceuticals in the treatment of metastatic bone pain. J Cancer Res Clin Oncol 2005;131:60-6.6. Palmedo H, Manka-Waluch A, Albers P, et al. Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: tandomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethyliden-ediphosphonate. J Clin Oncol 2003;21:2869-75.

S-24




029-GERClinical Results of Intravenous and Intra-Arterial Peptide Receptor RadionuclideTherapy (PRRT) using Y-90 and Lu-177 DOTA-TYR3-OCTREOTATE (Y-90 DOTA-TATE) in 151 patients with metastatic progressive neuroendocrine tumors (NET)Baum RP, Söldner J, Strauß H-JDept. of Nuclear Medicine / Center for PETCT, Zentralklinik Bad Berka, Germany

We investigated the anti-tumor efficacy and adverse effects of the somatostatin analog octreotate labelled with Y-90 or Lu-177 in patients with progressive neuroendocrine tumors and severe tumour burden.151 patients (69 f and 82 m, age range=19-81 yrs), 307 administrations, Mean activity per cycle 3.35 GBq (max. 7000 MBq) and time between cycles 3 to 6 months. 7 pts received intra-arterial injections (8 cycles). All patients were selected based on high SST-R expression as proven by immunohistochemistry and Ga-68 DOTA-NOC receptor PET/CT or somatostatin scintigraphy. Restaging was done using Ga-68 DOTA-NOC PET/CT, MRI, FDG-PET/CT, SST-R

Figure-1. Intra-arterial Peptide Receptor Radiotherapy using Y-90 DOTA-TATE

scintigraphy, F-18-Fluoride-PET/CT, renal scintigraphy (MAG 3), GFR measurements (DTPA) and monthly laboratory tests (haematology, liver enzymes, renal parameters, tumour markers). (Figure-1 and 2)Results revealed 2 patients with complete remission (de novo therapy), Partial remission (PR) in 37 %, Stable disease (SD) in 52 % and disease progression (DP) in 11%. Objective tumour response (including improvement of symptoms) was seen in 85 % of the patients. A few adverse effects were also noted: Nausea and vomiting occurred in 35 % of female, and in 15 % of male patients. Anemia, leucocytopenia and thrombocytopenia (G2-3) observed in less than <15 %. None of the pts developed myelodysplastic syndrome. No hair loss was observed.We conclude that PRRT with Y-90/Lu-177 DOTA-TATE results in a high response rate with significant improvement of clinical symptoms; the treatment is tolerated with low toxicity and few adverse effects and shows promising results also in pts with progressive neuroendocrine tumours after biological treatment (interferon/sandostatin) or after chemotherapy. Renal toxicity can be reduced by prolonging the intervals between therapy cycles and reducing the maximum activity per cycle (“Bad Berka concept”).

S-25



Figure-2. Intravenous and Intra-arterial Peptide Receptor Radionuclide Therapy (PRRT)

030-GERRadiosynovectomy in the Treatment of ArthritisKnut LiepeDepartment of Nuclear Medicine, University Hospital Dresden, Germany

Radiosynovectomy is a useful therapeutic option that involves radiopharmaceutical injections into joints, especially to treat rheumatoid arthritis. The indications included different kinds of arthritis, such as rheumatoid arthritis, psoriatic arthritis, Bechterew's disease, hemophiliac arthritis, osteoarthritis, but also patients with joint prosthesis and synovial effusion. There are three commercial available radiopharmaceuticals for the treatment: yttrium-90 for the knee (185 to 250 MBq), rhenium-186 for larger joints (shoulder and hip with 111 MBq; elbow, wrist, ankle joint with 74 MBq) and erbium-169 for smaller joints (acromioclavicular joint with 37 MBq, thumb base and MTP I with 30 MBq, MCP and MTP II-V with 22 MBq, PIP with 18.5 MBq, and DIP with 15 MBq, respectively). Decisive for the treatment is a positive sign for arthritis in the two-phase bone scan with 99mTc-HMDP (high uptake in the blood pool phase). Only for radiosynovecotmy in the knee an ultrasound with an evidence of effusion is sufficient. Side effects by the treatment are rare, such as temporary radiation or crystal synovitis, tissue necrosis (extra-articular fraction or intra-articular), joint infection (1 of 35,000 joints) or effects due to the immobilisation (thrombosis,

pulmonary embolism (immobilization of the knee), lymphoedema or loss of motion. In the treatment of the knee a prophylaxis with heparin is necessary to protect the patients for a pulmonary embolism.The clinical outcome is depending from the primary disease and the stage of arthrosis. Kresnik at al (1) reported in 2190 treated joints an overall response rate of 73 ± 17%. A higher response rate was observed in patients with early stage of arthrosis (73 ± 12%) to patients with advance stage (52 ± 24%). The best results had patients with hemophiliac arthritis (91 ± 4%). In our hospital were treated up to 10.000 joints with a mean response rate of 70-80%. There was a higher response rate in larger joints with 81 ± 5% (knee, ankle joint, shoulder and wrist) in comparison to the smaller joints with 74 ± 4% (MCP, PIP, DIP, thumb base, MTP). Unfortunately, 67% of the treated joints are small joints, especially in patients with rheumatoid arthritis. The duration of response ranged from 3 months to > 6 years. In patients with rheumatoid arthritis the duration of response is depends from the activity and the stage of the disease and these patients need an effective disease modifying treatment. Also patients with advance stage (Larsen 4) showed partial good results, especially patients with haemophiliac arthritis.In large centres the radiation protection for the medical staff is important. We observed a high beta dose of 22.1 µSv/MBq for the forefinger using only a syringe protection in treatments of knees ( 90Y), this resulted in a annual radiation dose > 1000mSv for 250

S-26



treated knees (normal for large centres). The high finger exposure in treatment of the knee (Y-90) could be reduced by around 95% using a simple manipulator (holding-forceps) for the fixation of

90the needle during the administration of the Y (2). The radiosynovectomy is safe if it performed by trained staff. We observed only one patient with joint infection in the time of introducing the procedure and no case with radionecrosis.Summary: Radiosynovectomy is an effective and fast procedure in the treatment of arthritis with a low rate of side effects.

References1. Kresnik E, Mikosch P, Gallowitsch HJ, et al. Clinical outcome

of radiosynoviorthesis: a meta-analysis including 2190 treated joints. Nucl Med Commun 2002; 23:683-8.

2. Liepe K, Andreeff M, Mielcarek J, et al. [Beta-radiation exposure at the finger tips during the radionuclide synovectomy]. Nuklearmedizin 2003;42:104-8

Peptide receptor radionuclide therapy (PRRT) is used in our department since 5 years (approx. 400 applications) for the treatment of patients with metastatic neuroendocrine tumors. Of all known peptides, the somatostatin analogue DOTA-NOC shows in vitro the highest affinity to somatostatin receptors (sstr) 3 and 5 and a very high affinity to sstr 2. We studied the in vivo behaviour of the two peptides DOTA-NOC and DOTA-TATE (highest affinity to sstr 2) by the use of different parameters like tumor and organ uptake, effective half-lifes (kinetics) and mean absorbed organ and tumor doses.We studied 27 patients with metastatic neuroendocrine tumors with high somatostatin expression, as verified prior to treatment by Ga-68 DOTA-NOC receptor PET/CT or somatostatin receptor scintigraphy (Tc-99m EDDA-Hynic TOC or In-111 OctreoScan, planar and SPECT). 22 patients (8M and 14F; aged 619 years) were treated with 2500 6790 MBq Lu-177 DOTA-TATE. Another 5 patients (1M and 4F, aged 6310 years) were treated with 4000 7400 MBq Lu-177 DOTA-NOC. Labelling efficiency and radiochemical purity using Lutetium-177 chloride (obtained from PerkinElmer Life Sciences, USA) were constantly over 99.5 %. Whole-body scans (anterior/posterior) were performed at 0.5h, 3h, 24h, 48h, 72h and 96h p.i. ROIs were drawn over the whole-body, organs, and different metastases (mainly in the liver). Blood samples were obtained in 12 patients after therapy with Lu-177 DOTA-TATE over 5 days for calculating the kinetics in blood.The ROI results were used to determine the uptake and effective half-life in different organs (kidney, spleen, liver, bone etc.) and the tumor residence times. By means of geometric mean, and after background correction, the ROI results were also used to calculate the estimated absorbed organ and tumor doses using the OLINDA software. Compared to Lu-177 DOTA-TATE (=100%), the uptake of Lu-177 DOTA-NOC was higher for the whole-body (45%) and for normal tissues (28%), and also in the spleen (11%) and in the kidneys (5%). In contrary, the uptake in the tumor was 13% higher

031-GERPeptide Receptor Radionuclide Therapy (PRRT) of Neuroendocrine Tumors: First Comparative Results using the Somatostatin Analogues Lu-177 DOTA-NOC and Lu-177 DOTA-TATEWehrmann C, Senftleben S, Baum RPDepartment of Nuclear Medicine / Center for PET-CT, Zentralklinik Bad Berka, Germany

for DOTA-TATE. For whole-body, the first effective half-time (t alpha) was longer 1/2

for DOTA-NOC (NOC 2.8+/-1.2h; TATE 2.0+/-0.6h), as well as the second elimination half-life (t beta) (NOC 58.0+/-11.0h; 1/2

TATE 53.9+/-13.6h). In normal tissue, the first half-time was longer for DOTA-NOC (NOC 3.0+/-0.8h; TATE 2.6+/-1.1h), however t beta was longer for DOTA-TATE (NOC 42.9+/-3.8h; 1/2

TATE 46.1+/-13.9h). The t alpha and beta were longer for 1/2

DOTA-TATE in the kidney (NOC 0.9+/-0.7h and 69.4+/-14.2h; TATE 1.6+/-1.4h and 74.9+/-34.8h, respectively). For the spleen, only t beta was calculated which was longer for DOTA-NOC 1/2

(NOC 74.5+/-3.2h; TATE 73.0+/-10.6h). In metastases, the second half-time was slightly shorter for DOTA-TATE (NOC 78.0+/-7.6h; TATE 75.0+/-25.0h).The resulting whole-body dose was lower for DOTA-TATE (0.20 Sv) as compared to DOTA-NOC (0.50 Sv). There were no significant differences between both peptides concerning the mean absorbed kidney dose (3.0 Gy) and the absorbed dose in the spleen (5.0 Gy). The mean absorbed tumor dose was 58+/-59 Gy for DOTA-TATE and 28+/-18 Gy for DOTA-NOC. The kinetics in blood showed a great variation (Table 1).These first results demonstrate that the higher in vitro affinity of DOTA-NOC leads to a higher uptake in normal tissues and therefore increases the whole-body dose. However, Lu-177 DOTA-TATE was superior to Lu-177 DOTA-NOC concerning the tumor dose due to the higher initial tumor uptake (esp. after 24 hours) and a very similar t beta in the metastases.1/2

These preliminary results have to be verified in future studies in a larger number of patients.

Intracoronary radiotherapy (IRT) with ß- and ?-emitters has been shown to reduce the rate of restenosis after percutaneous coronary interventions (PCI) and to have a beneficial effect on the clinical outcome of these patients (2). This presentation addresses the question whether IRT applied by open radionuclides is also able to achieve this aim: the Dresden prospective, RAndomized, placebo-controlled, double-blind, IN-stent restenosis trial (DRAIN) using the easy to handle, self-centering Rhenium-188 perrhenate liquid-filled standard PTCA balloon. In DRAIN 210 symptomatic patients (pts) for CAD with a mean age of 62 years (253 m, 166 fm) with in-stent restenosis underwent therapy (IRT) or sham procedure (SHP) with 45 pts in an initial pilot study. 165 pts were included then in the randomized part of the study from which 156 (95%) had 6-month quantitative angiographic follow-up. One-year follow-up was obtained from 164 pts. After routine re-PTCA a second standard balloon was placed into the PTCA area 5mm longer at each end than first balloon (5) and filled with ß-emitting liquid Re-188 at 3 atm. Geographical miss was carefully avoided. Irradiation time was 400 +/- 122 sec (range 240 to 890

032-GERIntacoronary Radiation Therapy: Placebo Controlled Study:A Report

1 2 2 3Kropp J , Reynen K , Koeckeritz U , Knapp FF1Deptt. of Nuclear Medicine, CTK Hospital, Cottbus, Germany; 2Deptt. of Cardiology, University Hospital Dresden, Germany; 3Nuclear Medicine Program, ORNL, Oak Ridge, USA

Half-time 1 Half-time 2 Half-time 3 Residence Time Red Marrow Dose

in h in h in h in h in Sv

Mean 0.25 1.78 17.96 0.13 0.18

STD 0.22 0.77 10.81 0.04 0.09

Min 0.07 1.05 6.19 0.09 0.10

Max 0.77 3.29 35.73 0.20 0.40

S-27



sec) to achieve a dose of 30 Gy at 0.5 mm depth of the vessel wall which seem to suppress the growth of smooth muscle and endothelial cells which are considered to be mainly responsible for restenosis (3). All patients had long-term strong antiplatelet therapy after IRT of at least 1 year (4).

All procedures were performed without any problem (Figure 1)In the pilot study consisting of 45 pts (group I: 25 pts only IRT, group II: 20 pts IRT+new stent) the restenosis rate in the second group was 63 % compared to the expected rate of 60% whereas in the first group the rate was 20 % (p < 0.03) which is in agreement with other studies (1). Therefore in DRAIN IRT + new stent was avoided in the following randomized study (Figure 2). In our randomized study two episodes of stent thrombosis with subsequent MI occurred in follow-up (after 6 days in SHP; after 8 months in IRT). Overall restenosis rate was 35%, 19/78 (24%) in IRT and 31/78 (40%)in SHP (p=0.04) (Figure 2).

There was no preferred location of the restenosis. Mean diameter stenosis amounted to 42 +/-19% in IRT and 51+/-22% in SHP

Figure 1 Clinical situation in the catheter laboratory during IRT. ISAT:188Isotope ( Rhenium) storage and transfer unit

Figure 2A. Before PCI of in-stent restenosis and IRT

Figure 2B. 6 months after PTCA and IRT

(p=0.03). The late lumen loss was 0.25+/-0.38 in IRG and 0.39+/-0.40 (p<0.05). At 1-year clinical follow-up overall event-free survival (death, MI, TVR) was 87 % in IRT and 74% in SHP (p < 0.05). All other parameters were not significantly different in both groups, but diabetes was even more frequent in IRT (44% vs. 27%).In conclusion, intracoronary radiation therapy with ß-emitting rhenium-188 liquid-filled balloon is an easy to perform, inexpensive, safe and effective option to prevent re-restenosis in cases of (re)stenosis. But only patients with in-stent restenosis seem to benefit clinically from the procedure during long-term follow-up if TLR, TVR and MACE are considered as endpoints.

References1. Cheneau E, Wu Z, Leborgne L, Ajani AE, Weissman N,

Pichard AD, Satler LF, Kent KM, Mintz G, Waksman R. Additional stenting promotes intimal proliferation and compromises the results of intravascular radiation therapy: an intravascular ultrasound study.Am Heart J 2003; 146(1): 142-145

2. Grise MA, Massullo V, Jani S, Popma JJ, Russo RJ, Schatz RA, Guarneri EM, Steuterman S, Cloutier DA, Leon MB, Tripuraneni P, Teirstein PS. Five-year clinical follow-up after intracoronary radiation. Circulation 2002; 105: 2737-2740

3. Henning E, Dittmann H, Wiskirchen J, Bantleon R, Kehlbach R, Claussen CD, Duda SH. Dose dependent effects of the

188combined beta-gamma-emitter Rhenium on the growth of human vessel wall cells. Fortschr Roentgenstr 2004; 176:404-408

4. Krötz F, Schiele TM, Zahler S, König A, Rieber J. Kantlehner R, Pöllinger B, Dühmke E, Theisen K, Sohn HY, Klauss V. Sustained platelet activation following intracoronary beta irradiation. Am J Cardiol 2002; 90:1381-1384

5. Syeda B, Siostrzonek P, Schmid R, Wexberg P, Kirisits C, Denk S, Beran G, Khorsand A, Lang I, Pokrajac B, Potter R, Glogar D. Geographical miss during intracoronary irradiation: impact on restenosis and determination of required safety margin length. J Aam Coll Cardiol 2002; 40:1225-1231

S-28



033-GERRadionuclide Therapy of B-NHL with Y-90 Epratuzumab: A Report of the Multi-Centre trial

5 1 2 3 3Kropp J , Chatal JF , Harousseau JL , Griesinger F , Meller J , 4 4 5 6Freundschuh MP , Kirsch CM , Naumann R , Huglo D ,

6 7 7 7Morschhauser F , Lateiner J , Wegener WA , Horak ID and 7Goldenberg DM ;

1 Institut de Biologie, INSERM, Research Unit 4, Nantes, France; 2Service d'Hematologie, Centre Hospitalier Universitaire, Nantes,

3France; Georg August University, Göttingen, Germany; 4Saarland University Medical School, Homburg/Saar, Germany; 5 6University Hospital Dresden, Dresden, Germany; Centre

7Hospitalier Régional Universitaire de Lille, Lille, France and Immunomedics, Inc, Morris Plains, NJ, United States.

The advantages of increased efficacy of RAIT compared to the naked antibody are at expense of temporary reversible bone marrow suppression. An ongoing, phase I/II, multi-center, dose-escalation trial in patients with relapse of a B-NHL is assessing safety and efficacy of Y-90-epratuzumab administered weekly for 2 or 3 consecutive weeks to achieve relatively high fractionated Y-90 doses (> 5 mCi/kg BW). Patients with indolent and aggressive NHL who failed prior therapy were eligible for this study. Thirty-seven patients have been revealed into two dose groups without

90 2achieving MTD (total Y dose, 30 mCi/m ) There were 18 .

follicular, 10 mantle cell, and DLBC-NHL. In 16 cases there was a foregoing BMT. The therapy consisted of 2-3 weekly injections of

2Y-90-hLL2 in dose steps of 3x5 3x10 mCi/ m (high-dose group 2without BMT) or 2x2.5 mCi/m (low-dose group with prior BMT).

In the frame of the first infusion there was added In-111-hLL2 to check the targeting of the tumour by imaging at day 3-5 post injection. In the low-dose group in 2 cases there were hematologic DLT noticed so that in this group MTD was achieved. In the high-

2dose group at 3x 10 mCi/ m there was only one DLT obvious. Except these non-lethal cytopenias no significant toxcicity was noticed. Also a HAMA induction was not substantiated. Five patinets without additional toxcicity were treated a second time Of the 37 patients, 23 (62%) had an objective response (OR) by IWG criteria, including patients with indolent and aggressive disease [12/17 (70%) and 11/20 (55%), respectively], across histologies [follicular NHL, 13/18 (72%); DLBCL, 7/9 (78%); mantle cell, 4/10 (40%)], and in patients failing rituximab (10/16, 63%). Most ORs were complete responses (CR/CRu, 15/23), and with follow-up now available in 15 CR/Cru responders, all had responses > 23 mo, including 2 patients continuing > 2.5 yrs. Dose escalation continues after 5/6 patients (83%) in the last cohort

2receiving 10 mCi/ m x 3 weekly infusions had an objective response, including 4 patients with CR/CRu. In conclusion, this

90fractionated schedule of Y-labeled humanized anti-CD22 antibody appears safe and efficacious in patients with recurrent NHL. Dose escalation continues after achieving 65% complete

2 90responses at a 30 mCi/m cumulative Y-dose. 034-GRELabeling of a Bombesin Analog with Rhenium-186Koumarianou E, Bouziotis P, Zikos C, Mitsokapas N, Xanthopoulos S, Varvarigou AD, Archimandritis SCN.C.S.R."Demokritos", Neapoleos & Grigoriou E, 15310 Aghia Paraskevi Attikis, P.O.Box 60228, Hellas, Greece

The need for the development of a new generation of radiopharmaceuticals with mainly therapeutic applications has led

our scientific team to label a novel Bombesin (BN)-like peptide with Re-186. The new derivative under study is: Gly-Gly-Cys-Aca-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-CONH2, where Aca: 6-amino-hexanoic acid (BN1.1). Rhenium-186 is an attractive radioisotope for targeted radionuclidic therapy because of its short half life (T1/2 =89.4h), its ß-particle emission (Eß = 1.07MeV, Eß = 0.93MeV) and its ?-emission (E? = 122KeV, E? = 137KeV, E? = 630KeV and E? = 768KeV) suitable for simultaneous external measuring. In the present work we have developed and studied the methodology for the labeling of BN 1.1 with 186Re of high specific activity. We have studied the labeling conditions in relation, to the production date of 186Re and to the pH of the Rhenium solution. We have also studied the labeling yield in relation to the pH, the concentration of the reducing agents and the quantity of the peptide derivative. The radiolabeling yield was checked by High Performance Liquid Chromatography (HPLC), and by Instant Thin Layer Chromatography (ITLC-SG). The obtained labeling yield was more than 95% with high radiochemical purity. The stability of the product was studied at different time intervals and storage conditions. The radiolabeled product is stable for at least 96 hours post labeling. Preliminary biodistribution experiments in normal and pathological models are in progress. We conclude that Rhenium186 is an attractive radioisotope for therapeutic use in radiopharmaceuticals, due to its nuclear characteristics. The bombesin analog BN1.1 has already shown a fine targeting behavior in biological models when labeled with 99mTc. For all the above reasons we chose to label and study the peptide derivative BN1.1 with Re-186. The radiolabeling process has yielded a stable and promising radiolabeled biomolecule which can be used for targeted radiotherapy.

035-GREPatient-specific Dosimetry of I-123-mibg in DiagnosisFor Improvement Of Dose Estimation in I-131-Mibg Adrenal Tumours TherapyLyra M, Phinou P, Papanikolos G, Jordanou J, Limouris G,Vlahos LDepartment of Radiology, University of Athens, Athens, Hellas, Greece

In this paper we present a patient-specific dosimetric approach using scintigraphic data from children undergoing diagnostic examinations with I-123-MIBG in order to estimate the adsorbed dose in a therapeutic treatment with I-131-MIBG and to administer the optimum dosage to each patient specifically. I-123-MIBG and I-131-MIBG scintigraphy has been established as a primary method for localization of lesions in patients with neuroblastoma. Dosimetric considerations (long physical half-time of 8.04 d and beta emission) limit the amount of I-131-MIBG administered for diagnostic purposes. Moreover, the gamma camera efficiency of detection of the 364 keV photon of I-131 is significantly low. This makes I-123-MIBG (with a short half-time of 13.2 h and a useful gamma energy of 159 keV), the diagnostic adrenomedullary scintigraphic agent of choice, with a sensitivity of 88.5% and a specificity of 98.5%. Adult biokinetic data used for absorbed dose estimates in children, introduce another inaccuracy parameter for dosimetry.In a series of 16 children, examined diagnostically by I-123-MIBG for neuroblastoma, the calculation of tumour doses was achieved by accurate quantification of planar scintigraphy, repeated twice for each patient, before therapy decision was made. The biodistribution of the compound was also studied in the

S-29


children with neuroblastoma undergoing a diagnostic administration of I-123-MIBG.Our methodology was to administer to the patient a diagnostic dose of I-123-MIBG of known activity and measured in counts by g-camera under a standard geometry- , for scanning imaging. Thyroid uptake of liberated radioiodine was also restricted by blocking it with stable iodide. Using scans we recorded the individual patient's biokinetics und uptake of the radiopharmaceutical, calculate tumour and critical tissues' dose and extrapolate the results to therapeutic administered activities of I-131-MIBG that was predicted to deliver a predefined whole-body dose. Phantom measurements of scatter and attenuation for both I-123 and I-131 radiopharmaceuticals were completed to get an energy correction factor.Total body scintigrams of I-123-MIBG were taken; regions of interest in the scans were determined to measure counts, counts per pixel and areas. Difference of attenuation between the two isotopes (I123 and I-131) was corrected. Using the MIRD formalism, a single exponential fit drawn through the data from the I-123-MIBG scans was realised. The increased adrenal uptake in pathological cases results in increase of absorbed dose in adrenals and other target organs affected by them.Both I-123 and I-131-MIBG are normally taken up by liver, spleen, myocardium and salivary glands. The normal adrenal glands are usually not seen, however a faint uptake may be visible 48-72 h after injection in up to 16% of cases. The hepatic uptake is maximal at 24 h and reduced in very low levels by 72 h.The results indicate substantial inter-patient variation in hepatic dose delivery, a fact that renders this organ critical in patients undergoing radiotherapy with I-131-MIBG. A patient-specific dosimetric approach using scintigraphic data from children undergoing diagnostic examinations with I-123-MIBG was completed. Assuming that the liver uptake remains approximately the same in the diagnostic image of a pathological subject, while the adrenals uptake is much increased, the ratio of liver to adrenals activity concentration measured in the ROIs of planar scintigrams, can give the altered adrenal uptake for each pathological subject. Using established MIRD data, but correcting for the increased adrenals uptake, the total absorbed dose to adrenals and other organs and tissues was calculated.In our series of 16 children, the median tumour dose was 3.2 mGy/MBq, however the variation in dose was great with values reaching up to 20 mGy/MBq in some patients. Whole body median dose was found to be 0.12 mGy/MBq and therapeutic ratio varied between 120 to below 40 in our patients. The adrenals absorbed dose in pathological cases was increased from 8 to 25 times. In conclusion, our aim was to determine the accuracy of using data from I-123-MIBG scans to calculate whole-body dose of the ensuing I-131-MIBG therapy. The use of I-123-MIBG in diagnosis and I-131-MIBG in therapy of tumours, originating from the neural crest, shows high sensitivity and specificity and good therapeutic efficacy with minor toxic side-effects to critical tissues. A dosimetry technique has been developed, employing quantification of gamma camera scintigrams that allow the estimation of tumour uptake and dose before and after therapy procedure. However, the wide deviation of dosimetric results between the various patients, coupled with the fact that the patients involved were children (radiation-sensitive population), emphasize the need for patient-specific dosimetry methods to be performed, recording dose burden and optimizing therapy outcome.

036-GREComparative Study of Skeletal Dosimetry Methods in Therapeutic Schemes with Re186 HEDP and Sm153 EDTMP Papanikolos G, Lyra M, Kontogeorgakos D, Jordanou J, Vlahos L, Limouris G Nuclear Medicine Division, Radiology Department, Aretaieion Hospital, Athens, GREECE

037-INDRadiation Synovectomy Versus Intra-articular Steroid Treatment in Inflammatory Arthritis.Solav S. SPECT Lab, Nuclear Medicine Services, Opposite Mangeshkar Hospital, Pune, India

Optimum therapeutic management of patients suffering from metastatic bone pain, requires accurate calculations concerning absorbed dose by metastatic lesions and other critical organs, such as red marrow. Mean absorbed dose, which is the current parameter used to predict the efficacy of the treatment, can either overestimate or underestimate, actual doses delivered in these organs/tissues of interest (TOIs). This study presents differences in dosimetric calculations derived utilizing parameters from different sources (MIRDOSE3, MIRD Pamphlet No 11 and S values published by Bouchet et al.), in therapeutic schemes with Re186HEDP and Sm153EDTMP. A set of planar scintigraphic images for 2 groups of patients (1 for Re 186 patients and the other for Sm153 patients) were obtained in the following sequence: 2 during the first 24h post injection (the last of which at 24h post injection) and 2 more from 24h 7d post injection. Processing of the obtained images utilizing ROI quantitative methods, previously calibrated with waterphantom measurements, determine residence times and radionuclide uptakes not only by TOIs but by specific skeletal sites as well. Dosimetric calculations were performed using MIRDOSE3 computer code, S values from MIRD Pamphlet No 11 and site specific Re 186 and Sm 153 S values for several source target combinations within trabecular and cortical bone, reported by Bouchet et al. (J Nucl Med 2000; 41:189 212), along with cumulative site specific activities derived from values obtained by image processing. Skeletal averaged Re 186 and Sm 153 S values were also used from the aforementioned study by Bouchet et al. Time activity curves for various skeletal sites were generated for both groups of patients. Absorbed dose distributions along with time dose rate curves were derived for both red marrow and different regions of the skeleton. Comparisons are made between these parameters and mean absorbed doses calculated using skeletal averaged S values, S values from MIRD Pamphlet No 11 and MIRDOSE3 computer code. It was concluded that mean absorbed dose calculations, in several cases, result in overestimations and underestimations concerning actual doses in TOIs. Knowledge of dose distribution and time dose rate curves in TOIs are crucial parameters for the assessment the relative biological effectiveness of either an ongoing treatment or a treatment about to start. They can also predict the possibility of dose escalation through multiple administrations of the two radiopharmaceuticals.

Two groups of patients were treated with intra-articular radio-isotope (Group-I) and steroids (Group-II) between Nov 2003 and December 2004. There were 25 patients (21 males, 4 females; Age range = 12-77 years) in Group-I and 28 joints were treated. All the

S-30



than three months projected survival. The documented primary tumours included cancers of the prostate (n=31), breast (n=46), lung (n=3) and others (one each of ovary, germ cell tumour of testis, oesophagus, primitive neuroectodermal tumour, Wilm's and multiple myeloma). Patients were administered the dose on an outpatient basis. 1 mCi/kg body weight of Sm-153 EDTMP (obtained from Bhabha Atomic Research Centre, a division of the Department of Atomic Energy, Government of India; radiochemical purity >98 %) was given by slow intravenous injection, followed by a whole body scan after 2 hours. All patients were followed up for 16 weeks post-therapy. For primary data analysis the end points of the study were the VAS results and analgesic consumption. The VAS pain score, analgesic score, mobility index and Karnofsky performance scores were recorded at 4, 8, 12 and 16 weeks, taking the mean of weekly scores, patients were closely followed for onset of pain relief and duration of response. If the pain intensity on the VAS decreased for at least two steps for two weeks, while the analgesic score remained at least constant; therapy with Sm-153 was considered as efficacious and the patient was a responder. If the pain score or analgesic score increased during the follow up period, the patient was considered a non responder. Toxicity was evaluated by measuring changes in platelets, leucocytes and haemoglobin during the first 12 weeks of follow-up and was classified by the 5-point toxicity score according to World Health Organization criteria. Overall response rate was 73 %; the responders showed an improvement in general condition and a better quality of life. Therapeutic effect started 4 to 14 days after administration with an average of 8.8±5.3 days. The effect lasted for 2-8 months; mean duration of response was 3.16±1.88 months. Approximately 12 % of patients were completely pain-free for a period of time. A total of 46 patients (44 females and two males, age range 32 to 80 years) with Ca breast and painful bone metastases were included for therapy. Six patients had complete response to therapy (complete absence of pain) and were not on any analgesic at the end of the four month evaluation period. Subsequently two of these patients received a second dose and three patients received three doses of Sm-153. 31 patients had partial response to therapy with a decrease in pain score and a decrease in the dose of analgesic medication required. Statistically significant reduction in pain scores and analgesic scores from baseline were seen at 4, 8, 12 and 16 weeks post-therapy. The Karnofsky scale improved in all responders. Generally improved mobility accompanied an improvement in pain scores. Nine patients did not respond to therapy with an increase in pain scores and analgesic index. 31 patients with hormone refractory Ca prostate, age 63±8.3 years (range 50 to 80 years) were administered Sm-153 therapy. Four patients had complete response to therapy and were not on any analgesics at the end of the four month evaluation period. Subsequently two of these patients received a second dose and two patients received three doses of Sm-153. 21 patients had partial response to therapy with a decrease in pain score and a decrease in the dose of analgesic medication. Statistically significant reduction in pain scores and analgesic scores from the baseline data were seen at 4, 8, 12 and 16 weeks post-therapy. The Karnofsky scale and mobility scores improved in all responders. Six patients did not respond to therapy. The response rate in Ca breast and Ca prostate patients was 80.4 % and 80.6 % respectively. Two Ca lung patients and one case each of ovarian carcinoma, germ cell tumor testis, cancer oesophagus, primitive neuroectodermal tumor, Wilms tumor and multiple myeloma did not respond to therapy. Haemoglobin, platelets and WBC decreaed by approximately 13

joints had evidence of synovitis on soft tissue scintigram. Infection and mechanical instability were excluded in all the cases. Out of 28 joints included in the study, 26 joints were treated with Yttrium-90 colloid and 2 with Rhenium-186 sulfide. The longest duration of follow up was one year in six joints and the shortest duration of follow up was three months in two joints. None of the patients in Group-I developed any complication such as infection, bleeding or local skin burn.There were 20 patients (14 males and 6 females; Age range = 32-76 years) in Group-II. All patients were proven cases of Rheumatoid arthritis and had evidence of local synovitis on soft tissue scintigrams.Pre and post treatment scorings were done by the consultant who was not involved in the treatment of the joints. Scoring was done using a visual analogue scoring system using a scale of 1-10, with “0” being no relief, “5” being 50% relief and “10” being complete relief. The results are summarized in the following table:

In the radiosynovectomy group, it was observed that there was escalating improvement in the relief from 32% at one month to 73% at six months. The second group revealed prompt relief of symptoms in the early period, i.e. at 4 weeks and there was resurgence of symptoms in majority of the joints at six months.

Systemic therapy with radionuclides may be the choice of treatment for palliation of metastatic bone pain owing to its efficacy, low cost and low toxicity. Imported radionuclides for pain palliation, like Sr-89 are expensive; particularly for developing countries. In the Indian scenario, Sm-153 is produced in our own reactors as a result of which it is readily available and economical. The objective of this study was to determine the efficacy of Sm-153 therapy for bone pain palliation in Indian patients with multiple skeletal metastases refractory to other modes of therapy. From April 2001 to September 2004, 110 patients were enrolled in the study, of whom 86 patients completed the 16-week follow-up. Inclusion criteria for the patients were: two or more sites of painful bone metastases corresponding to positive sites on bone scintigraphy, progressive pain requiring increasing level of analgesics, Karnofsky performance score of = 60, recurrent pain in a radiotherapy field, normal renal function, normal liver function, platelet count greater than 100,000/cu. mm, leukocyte count greater than 4000/cu.mm. Patients were excluded from the study if they had extensive soft tissue metastases and less

038-INDSm-153 EDTMP Therapy for Bone Pain Palliation in Skeletal Metastases: AIIMS Experience.Tripathi M, Chandrashekar N, Kumar R, Julka PK, Bal CS and Malhotra ADepartment of Nuclear Medicine, AIIMS, New Delhi, India

No of joints RS Steroid Chi- Significance

with >/= Group Group square

50% pain (N=28) (N=20) (X^2)

relief

At 1 month 9/28 16/20 8.87 P<0.01

(32%) (80%) (significant)

At 3 13/28 0/20 10.5 P<0.01

months (46%) (0%) (significant)

At 6 19/26 1/20 18.6 P<0.001

months (73%) (5%) (Highly

significant)

S-31



%, 23 % and 26 % respectively from baseline values with nadir at 3-4 weeks and recovery by 6-8 weeks. Grade 3 and 4 haematological toxicity was not seen in any patient. Only one patient experienced a flare response, though this was not associated with a clinical response to therapy. The results of the study showed that Sm-153 EDTMP offers a safe and effective treatment option in Indian patients with painful bone metastases. It is a well-tolerated single-session procedure that usually achieves good pain palliation and sometimes pain-free periods lasting several months.

Tumor therapy is constrained by demand to limit damage to normal tissue while arresting or at least slowing the growth and spread of tumor. Chemotherapy and radiotherapy from external sources are restricted by the harm they may impose on essential body function. Dimercapto-succinic acid, a dithiol (containing two sulfhydryl, or -SH, groups), is an analogue of dimercaprol and

99mused for metal chelation. Tc(V) DMSA localize in neurogenic and neuroendocrine tumors. Microsphere based carrier system

localize radiation dose to tumor sites and may eliminate the toxic side effects that are accompanied with systemic administration of radiation dose. The present study focuses on the characterization

188and in-vitro and in-vivo ability of Re(V)DMSA microspheres as therapeutic modality for some tumors. A Tungsten (W-188-Re 188) generator obtained from ORNL (Oak Ridge National Laboratory, Tennessee, USA) allows us on-site production of a beta emitting therapeutic isotope (Re-188) for up to 6 months from a single generator. Use of DMSA is also cost effective. A solvent evaporation technique was used to encapsulate labeled and unlabeled DMSA in poly (lactic-co-glycolic) acid (PLGA) microspheres. Microspheres of different sizes were prepared. The size was demonstrated by scanning and transmission electron microscope. Drug loading was studied by differential scanning calorimerty (DSC) and thermogravimetry analysis (TGA) and by Infrared spectroscopy. Release studies by spectrophotometric analysis demonstrated the amount of labeled DMSA released from the microspheres. The effect of poly ethylene glycol (PEG) was also studied as PEG alters the surface properties of microspheres.

188Glioma cell were incubated with Re(V) DMSA - microspheres in 96 well plate to study the dose effect. The viability, that is, survival fractions were studied by MTT (Di- methyl thiazol di phenyltetrazolium bromide) assay. The glioma cells were

188incubated with different doses of Re(V) DMSA microspheres between 0 and 200 Gy in 20 Gy increments. MTT was reduced in the presence of mitochondrial dehydrogenase in living glioma cells and formed insoluble blue colored formazan crystals. The optical density of formazan correlates well with the proportion of viable cells in the well. The measurements were recorded at different time point till 120 h of incubation of glioma cells with 188Re(V) DMSA microspheres. PEG coated, uncoated and of

99mvaried sized microspheres encapsulated with Tc(V) DMSA were injected in rats for biodistribution studies.Microspheres size ranged between 200 nm and 20 µm. DSC

039-INDRe-188 (v) DMSA -PLGA Microspheres for Targeted Therapy of Neurogenic Tumors

1 1 1 1 2Shukla J , Kumar R , Malhotra A , Maulik SK , Varma IK , 1Bandopadhyaya Gp

Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi- 110029 INDIA, Center for Polymer Science and Engineering Indian Institute of Technology, Hauz Khas, New Delhi-110016, INDIA

studies showed that the DMSA inside the microspheres are present in either amorphous crystalline state or in sold solution state. The IR of released material from microspheres was similar to the IR of

99mof Tc(V)DMSA. This demonstrated that the chemical nature of drug is intact inside the microspheres. If PEG was added in the initial stage of preparation with PLGA, the initial burst was very high but if the microspheres were coated with PEG after preparation, initial burst was drastically reduced. It was found that there was significant reduction in overall survival of glioma cells at different point of time. There was a decreasing fraction of viable

188cells with increased absorbed dose. Thus irradiation by Re(V) DMSA microspheres caused cell death (actually a regression of cell division) and resulted the inability of glioma cells to divide. Biodistribution studies demonstrated that PEG coated microspheres did not concentrated in liver. Normally, a foreign particle upon injection is coated by blood components (opsonisation) and rendered 'visible' to the defence system of the body, the reticulo-endothelial system(RES). The kpuffer cells of the liver are extremely efficient at removing particles recognized as foreign. As a consequence, an injected microspheres were directed to a particular cellular sub-set in the liver through the process of passive targeting. PEG prevented opsonisation of microspheres. Microspheres more than 9µm in size were accumulated in lungs.

188We conclude that Re(V)DMSA is a therapeutic analogous of 99mdiagnostic radiopharmaceutical Tc(V)DMSA. Accumulation

and retention release were size dependent, however variation in drug release kinetics was observed after coating of microspheres differentially. For the treatment of tumors, we could tailor the microspheres of different size and surface properties. A large number of cells were killed with radiation emitted by 188 188Re(V)DMSA microspheres. The emitting Re(V)DMSA microspheres may be a logical choice for the treatment of neurogenic tumors of different organs.

Carcinoma Thyroid is the most common type of endocrine malignancy. Incidence of Ca thyroid in India is 11 - 35 per million populations. This disease is more common among females (2 to 3 time more than in males). It is disease of middle and old age with gradual increase in incidence rate with age. Many groups have conducted studies since 1937 on the uptake of radioactive iodine by the carcinoma of the thyroid and its secondaries before and after surgery and also on the short and long term effects of radioiodine on the human body. All these studies have conclusively established the use of I-131 as the treatment of choice for residual, well differentiated thyroid ca after surgery. One hundred and fifty-five post surgical patients of different types of Carcinoma of the Thyroid treated between January 1998 and August 2004 were taken up in this study. There were 109 (70%) females and 46 (30%) males in the age group between 15 and 79 years. Majority of the patients (121 78%) fell in the age group between 20 and 60 years. With our past experience we did not resort to low dose ablation advocated by certain groups. 149 (96%) patients fell in the differentiated group. Of these, 119 (77%) patients had Papillary Carcinoma. 135 (87%) patients were

b

040-INDOur Experience with the Treatment of 155 Cases of Carcinoma of Thyroid

1 2 2 3Anand YNI , Rajini TR , Sankar R . Muthu GS1 2“The Nucleus”, Mysore, India; Meenakshi Mission Hospital &

3Research Centre, Madurai, India; Tata Main Hospital, Jamshedpur, India

S-32



administered ablative doses of upto 100 mCi (3.7 GBq). Only those patients with multiple metastases were administered doses between 100 and 300 mCi (3.7-11.1 GBq). Two patients received total doses of more than 1 Ci (37 GBq). Two of the patients were not administered any dose of Radioiodine 131 post surgically. The follow up period varied between eight months and seven years. One hundred and twenty-nine (83%) patients needed a single dose for successful ablation of the residual thyroid tissue. 16 (10%) patients needed a second dose. Most of the other patients had multiple metastases at the time of diagnosis and hence needed three or more doses for ablation of residual thyroid tissue and treatment of metastases. Seven patients died during the period of review. 5 of them died due to causes directly related to Ca Thyroid or its consequences, thus giving a death rate of about 3%. All of them had either extensive local or distant metastases. This study reveals that almost all the patients are successfully ablated with doses upto 100 mCi (3.7 GBq) of 131I. Although, treatment of metastases was incomplete, we could control the disease in most of these cases. Survival rate was as high as 97% in our series at the end of seven years. Hence we recommend post surgical ablation of the residual thyroid followed by long term follow up of all cancer thyroid patients, including Anaplastic Ca.

The main objective of this study was to compare and correlate the information obtained from high resolution ultrasound (USG) and soft tissue scintigraphy in the evaluation of painful joint disorders and follow-up of patients after Radiosynoviorthesis.Thirty-two patients suffering from painful joint disorders including Rheumatoid Arthritis were prospectively studied. High resolution ultrasonography of joints was performed with a 15 MHz transducer. Soft tissue scintigraphy of joints were performed in a single head gamma camera with leap collimator 15-20 minutes after injecting 20-25 mCi of Tc-99m MDP. Anterior, posterior, lateral and if needed oblique views were obtained. Delayed images of joints were also obtained.High resolution USG demonstrated effusion, synovial proliferation, thickening, Backer's cyst and bone erosion effectively, and was very useful in guiding aspiration. On the other hand soft tissue scintigraphy was found to be more sensitive in detecting active synovial inflammation and showed excellent correlation with clinical features. The earliest changes after therapy were reduction in the intensity of uptake in soft tissue scintigraphy and reduction of degree of effusion in USG. Delayed phase bone scans were helpful for assessment of extent and severity of disease and deformity.We conclude that soft tissue scintigraphy is a better indicator of the active synovial inflammation having better correlation with clinical features. Hence it is better suited for selecting patients for radiosynoviorthesis. Ultrasound however was found to be a better tool for detecting and treating associated effusion. The earliest changes of treatment response were changes in soft tissue uptake and reduction of effusion

041-INDComparison of Musculo-Skeletal Usg And Radionuclide Soft Tissue Scintigraphy in The Evaluation, Selection and Follow-up of Patients for RadiosynoviorthesisRay S, Basak B, Dey NR, Sharma SKEco Nuclear Imaging Centre, Calcutta, India

0



42-INDImpact of FDG-PET imaging in the treatment of Lymphomas: Indian experienceKrishna BADepartment of Nuclear Medicine, P.D. Hinduja National Hospital, Mahim, Mumbai, India

043-INDTreatment of differentiated thyroid cancer using Recombinant TSH injectionKrishna BADepartment of Nuclear Medicine, P.D. Hinduja National Hospital, Mahim, Mumbai, India

S-33



044-INDOur Experience of High Dose I-131 Therapy in 75 patients with Well Differentiated Carcinoma Thyroid Followed Up Over 5 yearsDougall P, Kumar A, Ashok P, Chinwan BP, Khan B, Pandey D, Joshi ND. Sitaram Bhartia Institute of Science & Research, New Delhi, India

Thyroid cancer is the most common endocrine malignancy. The epidemiology of thyroid cancer is variable, depending on the geographic location of the patient population. Well differentiated thyroid cancer (WTC), is responsive to high dose I-131 treatment, and is the most accepted form of therapy, even though the dose administered for ablation of residual thyroid tissue maybe controversial.At our centre, 75 patients of WTC, mean age 42.4 years, 22 males & 53 females (M:F 1:2.4), were treated with high dose oral I-131 therapy with a Total Mean Dose (TMD) of 263.6 mCi, 4 - 6 weeks post thyroidectomy. They were followed up over a period of 6 years. Twenty ( 26.7%) patients had follicular cancer (FC), 47 (62.7%) papillary cancer (PC) and 8 (10.7%) were mixed (MC), on histopathology, at presentation. 38 (50.7%) patients had only residual thyroid tissue (RTT) on I-131 whole body bone scan (WBS) and 37 (49.3%) presented with metastatic disease (MD) at the time of therapy (Table-1). Of the 37 patients with MD, 21

(56.8%) had metastases to the lymph nodes, 6 (16.2%) to the lungs, 4 (10.8%) to bone, 3 (8.1%) to bone and lung, and 4 (10.8%) to lung plus lymph nodes (Table-2). Twenty-three patients (7 FC , 13 - PC & 3 MC; 6 RTT, 17 - MD) , received more than one dose of I-131 with a TMD of 422.7 mCi (Range 88 1590 mCi ). 52 patients (13 FC, 34 PC, 5 MC; 20 MD and 32 RTT) received a single TMD of 104.4 (Range 39.5 219 mCi) (Table-3).

On follow-up, 3 patients of FC with MD (2 lung metastasis and 1 with extensive lymph node metastasis), died within 3 months 2 years of therapy. 3 patients of MD (2 FC, 1-MC; 2 bone metastasis and 1 bone with lung metastasis) died after 5 .5 years, Of the 6 patients who died, 5 were FC and only 1 was MC. 2 patients with MD to lungs and bone had received a single dose and were lost to follow up. All patients with PC and FC with only RTT, were surviving at the end of 5 years. None of the patients with MD to lymph nodes died at the end of 5 years, either receiving single or multiple doses. In our study group, the TMD for ablation used in RTT was 100.4mCi, and 5 year mortality was zero. The patients with MD involving lungs and bone had the worst prognosis,

despite multiple doses of I-131 (TMD of 442.7 mCi). 33.3% patients with lung metastasis died before the end of 5 years. Only bone MD had slightly better prognosis than either lung or lung plus bone metastasis. Lymph node involvement did not increase the mortality, and it remained zero at 5 years.

In Radioiodine therapy wards, in general the radiation exposure due to air borne activity from patients administered with 925MBq-

1317.4GBq (25-200mCi) of I has to be kept under regulatory limits. The purpose of conducting an air monitoring in our setup was to assess air borne activity levels. If the levels are high then it may lead to increased exposure to the occupational workers and

131patient's attendants. A total of 22.2GBq (600 mCi) I is administered every week to our patients in the isolation ward.

131After administered of I in the dose administration room, patients occupy their respective beds. The isolation beds are provided with attached toilet facility. Six air samples were collected from various regions (high dose room, low dose room, dose administration room, special room, corridor and entrance) in the vaccumized vials (9 ml) using 16 G needle at the breathing zone level. One control sample was also collected from the area with no

131possible I air-contamination. The vials were then counted in the pre-calibrated NaI well counter (known efficiency).The maximum air borne radioiodine concentration was found to

-6 3be 1.999X10 ?Ci/cm in the high dose room (which keeps on decreasing with time, being maximum on second day and zero on third and subsequent days). We measured the thyroid counts of the staff and patient's attendants, routinely. The estimated thyroid activity never showed any significant increase in the thyroid uptake of the staff and patient's attendants. In our setup, air monitoring is strictly followed and performed periodically. We conclude that air monitoring program is only one element of the comprehensive radiation protection program and should be a made mandatory practice.

The aim of this study was to estimate the cytogentic damage to peripheral blood lymphocytes based on the incidence of micronuclei in 15 patients receiving radioiodine treatment for differentiated thyroid cancer.Blood samples (2ml) were taken from 15 differentiated thyroid carcinoma patients (2men, 13women; mean age 34y; range,18-52y) immediately before and after their radioiodine therapy. The administered activity varied from 925-5550MBq (25-150mCi). Whole blood lymphocyte cultures were set up for micronuclei assay consisting of 0.5ml of whole blood, 10g/ml of PHA-M, 10% fetal bovine serum. Cultures were incubated at 37C for 72hrs, with last 26hrs in presence of 6g/ml cytochalasin -B (Cyt-B) to arrest the cells at cytokinesis after the nuclear division is completed. Cultures were terminated and harvested after 72hrs using standard

045-INDAir Monitoring in Radioiodine Therapy WardSarika, Pant GS, Bal CSDepartment of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India-110024.

046-INDIncidence of Micronuclei as Biological Dosimetry in

131Differentiated Thyroid Carcinoma Patients Treated With I1 1 1 1 2Senthamizhchelvan S , Pant GS , Bal Cs , Malhotra A , Julka PK ,

2 2Nair O , Rath GK1 2Department of Nuclear Medicine, Department of Radiotherapy, All India Institute of Medical Sciences, New Delhi, India.

Papillary Follicular Mixed Total

Residual tissue 28 (59.6%) 5 (25%) 5 (62.5%) 38 (50.7%)

Metastatic 19 ((40.4%) 15 (75%) 3 (37.5%) 37 (49.3%)

Total 47 (62.7%) 20 (26.7%) 8 (10.7%) 75

Table 1 Histopathology of disease in the study population

Lymph nodes Lung Bone Bone & lung Lung &Lymph node

Papillary (15)+2 (2) - - (2)Follicular (1)+3 (4)+5 (3)+3+1(LN) (3) (2)Mixed (5)+2 - (1) - (1)Total 21 (56.8%) 6 (16.2%) 4 (10.8%) 3 (8.1%) 4 (10.8%)( ) single organ involvement + additional organ involvementTable 2 Distribution of metastatic disease in the study population

Dose Follicular Papillary Mixed RTT MD TMD

Single 13 p 34 p 5 p 32 p 20 p 104.4 mCi

Multiple 7 p 13 p 3 p 6 p 17 p 422.7 mCi

20 p 47 p 8 p 38 p 37 p

Table 3 Number of patients administered single / multiple I-131 Dose

S-34




protocol and cells were spread in glass slides for staining and analysis. Micronuclei were scored in 1000 cytokinesis blocked (CB) cells for each sample. The effective total body dose (ETBD) was estimated for all patients from previously obtained in vitro Co-60 dose- response curve.The incidence of micronuclei before and after therapy was 198 (mean S.D) and 3210 (mean S.D) respectively. The ETBD in these patients ranged from 16.3 33.8 mGy (mean S.D; 21.54.8).The negligible amount of cytogenetic damage to peripheral blood lymphocytes could be due to low iodine uptake, the small size of

131remnant tissue and rapid washout of I from the body in thyroid carcinoma patients. Relatively low incidence of micronuclei after radioiodine therapy in this study as compared to external radiotherapy, reveals that there is less radiation risk/detriment to

131ca-thyroid patients treated with I.

131Radioiodine (I ) therapy as an adjuvant treatment in post surgical management of differentiated thyroid cancer is generally performed for achieving two intended objectives: to increase the specificity & positive predictive value of subsequent radio iodine scanning and serum thyroglobulin measurements for detection of recurrent or metastatic disease and to destroy any residual albeit undetected microscopic foci of malignant disease. Although it is more or less agreed that adjuvant treatment of differentiated thyroid cancer is required in most of the patients, the factors influencing optimum effective dose to achieve remnant ablation and at the same time reduce the chance of recurrence has not been well established. The current practice is to use either a low fixed dose for low risk group or a higher dose for the high risk group (based on clinical presentation, surgical and histopathological findings) or follow the dosimetric method of calculating the ablative dose. In this paper we have made an attempt to optimize the indictions and ablative radioiodine dose as an adjuvant treatment in differentiated thyroid carcinoma.Patients of differentiated thyroid carcinoma who underwent adjuvant treatment with radioiodine, in the last 5 years, were analysed. Patients with less than 12 months followup, extra thyroidal extension seen per operat ively or histopathologically and with evidence of distant metastasis at presentation were excluded from this study.

131The patients were divided into three groups as per the dose of I received as adjuvant treatment (1.85 GBq, 5.55 GBq & > 5.55 GBq). The end points were adequacy of remnant ablation and the outcome at the average followup period . Ablation was defined as total; near total or partial based on the findings of first followup scan 6 months post treatment. The outcome was evaluated by

131clinical examination; serum thyroglobulin estimation and I scan (after withdrawal of thyroxine) at subsequent follow up at an interval of 6 months. The status at follow up was based on all the above three findings. No gold standard was defined. A total of 78 patients were analysed. Age range was 17-72 yrs with an average age of 38 years & a female preponderance (62%). 77% of patients had papillary carcinoma, 8% follicular carcinoma & the rest was of mixed variety. 64 patients showed evidence of residual tissue only in the post operative radioiodine scan. 20% (13/64) of these patients had histopathological evidence of lymph node metastasis

047-INDOptimizing the Indications for Radioiodine Therapy as an Adjuvant Treatment in Differentiated Thyroid Carcinoma.

1 2Choudhury PS , Dewan AK1 2Departments of Nuclear Medicine & Surgical Oncology , Rajiv

Gandhi Cancer Institute & Research Centre, New-Delhi, India

post surgery. 51 patients ( 6 with nodal metastasis ) received 1.85 GBq (50mCi) and 13 patients received 5.55 GBq ( 150mCi) as ablative dose in a non randomized manner (group 1 and group 2 ). In the first group, 14/51 patients are awaiting their first follow up scan and thus not included in the analysis at this point of time. Out of the 37 patients, 24 (65%) achieved total ablation and 10 (27%) near total ablation.Significant persistent remnant tissue was seen in 3 (8%) cases and required a second ablative dose. 29/37 had an average follow up of 22 months. 1 case of ipsilateral neck recurrence was seen. In group two, 13 patients (7 with lymph node metastasis) received 5.55 GBq (150mCi). A single dose was adequate to ablate the residual tissue with an average 23 months disease free interval. In group three, 14 patients showed evidence of residual tissue plus lymph node metastasis in the radioiodine scan. These patients received a higher dose ranging from 5.55-7.40 GBq (150-200mCi).There was no fixed criteria for selection of a particular dose. 8/14 (57%) in this group required more than one treatment dose of radioiodine.

131The above results show that 1.85 GBq of I is adequate to achieve desired remnant ablation and an extended disease free outcome in the presence of only residual thyroid tissue post operatively. An

131I scan appears to be the single most important factor for deciding the ablative dose in this group of patients irrespective of the presence or absence of nodal disease during primary treatment. At this stage there appears to be no difference in the outcome of patients receiving low or high ablative dose in the above patient population. Whether there is a difference in the time to recurrence in these two different groups will need to be seen with a longer followup period . Evidence of nodal metastasis in the radio iodine scan generally preempts the need for higher and multiple radioactive iodine dose.

We present our initial experience of treating patients of hyperthyroidism with radioactive iodine (RAI) in the hilly area of India, which falls, under endemic zone of iodine deficiency (sub Himalayan zone). People here have largely switched over to iodized salt to supplement the iodine intake in the food. It has shown remarkable regression in goitre and thyroid disorders. RAI (I-131) has been in use successfully for more than 60 years for the treatment of hyperthyroidism that may be due to Graves' disease (diffuse toxic goitre), toxic multi nodular goitre or solitary toxic nodule. After the treatment with I-131, these patients are followed up at interval of 6 & 12 weeks initially followed by 3 months for the first year and then 6-12 months henceforth. This is the only facility to treat patients of thyrotoxicosis with RAI in our area. Physicians used to treat such patients with drugs or surgery before the availability of RAI (I-131). But with availability of the facility for administering RAI since mid 2000 and increased awareness regarding its advantage of definite treatment, low cost, and easy administration with better compliance in hilly area where regular follow-up and cost are quite consideration, has made it quite popular among the referring doctors. In our centre emphasis was made on the treatment options available to doctors and patients explaining the advantages vs. disadvantages for the various modalities. The objective of this abstract is to show the outcome of treatment given to patients since

048-INDRadioactive Iodine (I-131) in the Treatment of Hyperthyroidism in Hilly Terrains an Initial ExperienceSood A, Seam RKNuclear Medicine Centre, Regional Cancer Centre, Indira Gandhi Medical College, Shimla-171001, INDIA

S-35



so far.Total 108 patients referred for RAI treatment have been treated so far from August 2000 till March 2005 with 136 doses administered which consisted of 22 males and 86 females with age range from 28-64 yrs (mean age-43.1 yrs) and 19-70 yrs (mean age- 42.7 yrs) respectively. 87 patients were given single dose, while 21 patients required 2 or more doses to achieve euthyroid status. Re-treatment was done not before 3 months after first administration if there was evidence of residual disease on clinical and biochemical status. 15 of the 108 patients were excluded from this study, as their follow up period was less than 3 months. Remaining 93 patients underwent regular follow-ups. 33 out of these 93 patients developed hypothyroidism during the period ranging from 2.5 months to 42 months post RAI administration (35.5%). Majority of them (28/33) developed hypothyroidism with in 1 yr of post RAI (84.4%) while remaining developed hypothyroidism after 1 yr. Earliest appearance of hypothyroidism in patient was at 3 months that were promptly treated with L-thyroxin. Average amount of iodine-131 /dose given was 6.2 mCi. Doses of RAI (I-131) administered ranged from 3.3 mCi (minimum) to 20 mCi (maximum) in different patients during the course of treatment. All these patients are still undergoing periodic follow-up without any significant side effect. The result of this study shows that I-131 is safe and cost effective method to treat hyperthyroidism.

Medullary thyroid Carcinoma (MTC) originates in para-follicular cells in thyroid and belongs to the APUDOMA group of neuroendocrine tumors. It can be hereditary or sporadic variety. Hereditary variety can present in 3 forms namely-MEN II A, MEN II B and familial forms. All three forms have RET proto oncogene mutation. MEN II A include MTC, Pheochromocytoma and Hyperparathyroidism. MTC, Pheochromocytoma, multiple mucosal neuromas and ganglioneuromatosis of G.I.tract constitute MEN II B with marfanoid faeatures. We routinely exclude Pheochromocytoma by doing CT or US evaluation of abdomen with Urinary catecholamine estimation.To rule out familial variety we doing serum calcitonin for the siblings and also for children.The standard treatment for MTC is total thyroidectomy (TT) with or without Radical neck dissection depending on the individual caess.We evaluate these MTC with Tc99m DMSA(V) scans 3-4 weeks after TT . Serum Calcitonin is estimated and this is correlated with DMSA findings. If DMSA is abnormal the finding is correlated with regional CT sacn / bone scan. If lesion is found suitable the same is resected. Serum Calcitonin estimation forms the sheet anchor during follow-up of these patients. Whenever it is elevated DMSA scan is done. There is good correlation and high sensitivity between Calcitonin and DMSA findings. In few instances I131 MIBG scan were also done. Our experience in the past 5 years with about 25 patients are discussed.

049-INDEvaluation of Medullary Thyroid CarcinomaDr. R. Krishnakumar Department of Nuclear Medicine, Cancer Institute (WIA), Chennai-600020, India,

050-INDA Single Vial Method of Preparation of I-131 Meta-iodobenzylguanidine (MIBG)Snehlata, Tripathy M, Malhotra ADepartment of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India.

Metaiodobenzylguanidine (MIBG) labeled with I-131 is used for imaging neural crest derived tumors like pheochromocytoma and neuroblastoma as well as for the scintigraphic assessment of cardiac sympathetic neuronal integrity. Different methods of preparations of MIBG labeling with I-131 are available with variable success. In the present study we tried to label MIBG using ammonium sulphate facilitated exchange method.The radiolabeling procedure was based on ammonium sulphate facilitated exchange radioiodination of MIBG in an aqueous solution in a closed system. The radioactive yield of I-131 MIBG was found to be more than 90 % which was achieved in 30 minutes at 160-170 C. The concentration range of MIBG and ammonium sulphate was in the ratio of 1:10. Radiochemical purity, purity and stability of the labeled MIBG were checked.The reaction mixture was subjected to purification over an anion

-exchange column (Dowex-1 X 8,200-400 mesh, Cl form preconditioned with 4M HCl). RCP was checked by paper chromatography using Whatmann 1 and different solvent systems and found to be more than 98%. Stability of I-131 MIBG was checked by adding 1% benzyl alcohol and preparation was found to be stable for four days.These results show that I-131 MIBG can be prepared easily and rapidly using ammonium sulphate facilitated exchange method for diagnostic purpose. Because of simplicity of the method, it can be utilized in Nuclear Medicine Centers in developing countries.

Radioiodine therapy is an essential component of thyroid cancer management and these patients require life long follow up at timed interval. Though radioiodine therapy is a well established adjuvant treatment for well differentiated thyroid cancer, still the acceptance by the surgical colleagues and patients is not uniform. In addition, this facility is not available in the eastern part of the country. Therefore, such patients are required to travel more than 1500 K.M. to avail this treatment and subsequent follow up at our Institution. The existing telemedicine facility between SGPGIMS, Lucknow and SCB Medical College, Cuttack provided the opportunity to utilise the system for tele-consultation and tele-follow up of thyroid cancer patients.The rationale of this ongoing study is to evaluate the suitability of telemedicine for tele consultation prior to radioiodine therapy and tele follow up following radioiodine therapy of patients with well differentiated thyroid cancer.Thirty patients ( 10 new cases and 20 follow up cases) were included in this study. New cases were studied on the basis of case history inputs by the operating surgeon and direct patient consultation to find out their suitability for high dose radioiodine therapy. At the same time pre-therapy instructions as well as details of admission were finalised. Follow up of patients( 20 in number ) were discussed and examined on live along with operating surgeon with respect to compliance of thyroxine suppression therapy, local recurrence and need for further high dose radioiodine therapy. Each time, at least one surgeon and nuclear physician were involved during live evaluation of patients which was done with VSAT, broad band of 256 Kbps band width provided by ISRO, Bangalore, India and case history, radiological

051-INDTele Consultation and Tele Follow up of Thyroid Cancer Patients a Pilot StudyPradhan PK, Das BK, Mohanty BN, Mishra SKDept. of Nuclear Medicine and Dept. of Endocrine Surgery, SGPGIMS, Lucknow and Dept. of Experimental Surgery, S.C.B Medical college, Cuttack, INDIA

S-36


and nuclear medicine images were already transmitted prior to live evaluation.All ten new cases were found to be suitable for high dose radioiodine therapy. The appointment dates for their evaluation and admission could be finalised and instructions for withdrawal of thyroxin could be given to patients. Out of twenty follow up cases, only thirteen patients were required to come to SGPGIMS, Lucknow. Rest of the seven patients could be managed with instructions and need not travel to our Institution.Telemedicine has been utilised for follow up of patients in several areas. Gilmour et al emphasised the importance of telemedicine for diagnosis and management of dermatology cases referred from primary care. Fifty percent of patients could have been managed by single tele consultation without requirement of further specialist intervention. Alen et al reported the utilisation of telemedicine in cancer patients in rural areas. Redlick et al used telemedicine to evaluate patient and physician satisfaction with tele-consultations in follow up of burn cases and to assess the cost and benefit of tele-consultations. Patients were very satisfied with theirTele-consultations and found them more economical and time efficient than in person visits. Telemedicine technology has been utilised for diagnosis of thyroid disorders. However, tele-consultation and tele-follow up of thyroid cancer patients before and after radioiodine therapy has never been utilised as per published literature. This telemedicine tool has strong potential for consultations of patients with thyroid cancer and monitoring them subsequently at timed interval following radioiodine treatment.In our pilot study 100 % of patients consented and subsequently received radioiodine and 35 % of follow up patients did not visit our Institution at Lucknow because of live interaction through telemedicine.The tele-consultation and tele-follow up of thyroid cancer patients provided great degree of patient satisfaction because of direct audiovisual contact. Saving of travel expenses as well as inconvenience to travel such long distances could be achieved in 35 % of cases. This is substantial both in terms of direct and indirect expenditure as well as loss of working hours for the accompanying persons as prevails in our society. The satisfaction of the operating surgeon could be achieved by discussing individual cases with regards to further follow up and management.

Radioiodine therapy is the safest, simplest, least expensive and most effective method for treatment of Graves' disease. But optimal method for determining iodine-131 treatment doses for Graves' hyperthyroidism is unknown, and techniques have varied from a fixed dose to more elaborate calculations based upon gland size, iodine uptake, and iodine turnover. Due to difficulties in previous methods for dose determination, fixed dose method of I-131 is now considered the best practical method for I-131 therapy in Graves' disease, but there is no consensus on the dose. We compared two routinely recommended fixed doses of 185 and 370 MBq for this purpose. Methods and Materials: Patients with

052-IRAComparative Evaluation of the Two Fixed Dose Methods of Radioiodine Therapy (185 MBq and 370 MBq) for the Treatment of Graves' Disease.Esfahani AF, Fallahi B, Kakhki VRD, Eftekhari M, Beiki D, Saghari MResearch Institute for nuclear medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, I.R. Iran

Graves' hyperthyroidism (n = 59) who had not been previously treated with radioactive iodine were randomized in two groups of 185 MBq (5 Ci) and 370MBq (10 mCi). l patients were followed for two years, with 6-month intervals for following clinical outcomes: hyperthyroid requiring further radioiodine, and hypothyroid requiring life-long replacement therapy. Euthyroid and hypothyroid states were considered successful therapy (cure) and hyperthyroid state was considered failure (no response or relapse). Results: Totally, among 59 patients treated with I-131, 20 (33.9%) patients became euthyroid and 19(32.2%) became hypothyroid, while failed therapy was noticed in 20 patients (33.9%). In the group treated by 185 MBq (33 patients), 10(30.3%) were euthyroid, 6(18.2%) were hypothyroid (overall cure rate of 48.5%), while 17(51.5%) remained hyperthyroid by the end of the follow-up period. From the 26 patients treated with 370 MBq, the euthyroid and hypothyroid states were observed in 10(38.5%) and 13(50%) patients, respectively (overall cure rate of 88.5%), and hyperthyroid state in 3(11.5%). No relationship was noted between the outcome and age, sex, size of the thyroid gland and thyroid uptake, but the relationship between the disease outcome and the amount of administered radioiodine was significant (P<0.003).Discussion: Although the incidence rate of early hypothyroidism (by the end of 2 years) in the group treated with 185 MBq is less than those treated with 370 MBq, the incidence of failed therapy is higher in the former group. In addition, long-term hypothyroidism prevalence is not significantly different by using different doses ofI-131. On the other hand, if the initial dose is so little to cure, cost and time for perfect treatment, number of office visits and morbidity due to untreated hyperthyroidism are markedly increased. Conclusion: Regarding lower rate of failed therapy with 370 MBq, and as there is no significant difference in late hypothyroidism between low doses and high doses of I-131, we concluded that 370 MBq is the optimal fixed dose for treatment of Graves' disease.

Depression is a common disease in general population and may be more frequent in the cases of malignant diseases. Diagnosis and treatment of depressions in such patients may improve the quality of life. The aim of this study was to determine the risk of depression in patients diagnosed as differentiated thyroid cancers

131(DTC) and treated with radioactive iodine ( I).In a historical Cohort study, 390 DTC patients, 312 female and 78 male, 18-68 years with median age of 41 years who were treated

131with I and 390 control cases selected from the patients' relatives and matched with DTC cases by age, sex, wedding state and socio-economic status were entered the study. Each patient and his/her control were concurrently assessed with Beck's questionnaire for diagnosis of depression. The data was analyzed to detect the rate, severity and relative risk of depression and the effect of some variables on the severity of depression in these patients.Of 390 patients, 179(45.9%) showed some degree of depression, 20.3% mild, 14.1% moderate, 11% partially severe and 0.5% severe according to Beck score, while the proportional frequency of different grades of depression among the control group was

053-IRAThe Rate of Depression and its Risk Stratification in Patients With Differentiated Thyroid Cancers Treated With Radioactive IodineEftekhari M, Fallahi B, Ansari S, Izadian ES, Esfahani AF, Beiki D, Saghari MResearch Institute for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran

S-37



15.5% and overall relative risk of depression in DTC patients was 2.96. The frequency of depression in female patients, 47.8% was lesser than male, 38.5% (p=0.013) and in married female (46.2%) was greater than single (14.3%) but lesser than divorced or widow female patients (82.4%), (p<0.0001). Depression was more prevalent and more severe in cases of papillary, 47.9% than follicular carcinoma, 33.3% (p=0.014) and also was more predominant in less-educated than in high-educated patients (p<0.0001). In DTC patients with history of radio-iodine therapy, the rate of depression is almost three times of the general population, so screening and treatment of depression especially in high risk patients like married or divorced female and less-educated patients may be of great importance for improving the patients' quality of life.

Intravenous injection of Strontium-89 (Sr-89) is an accepted palliative treatment for bone metastases. We evaluated the pain relief achieved with this radiopharmaceutical in patients with widespread painful bone metastases from prostate and breast cancers. Pain intensity on a 9-grade scale and use of narcotics was recorded before and after Sr-89 injection, and the ensuing palliative effect was divided into complete, partial and no response. The duration of response was also recorded. Thirty-five patients with widespread painful bone metastases were treated with Sr-89, of whom 22 had prostate and 13 breast cancers. Mean follow-up was 227 days, during which death was recorded for 32 patients. Fourteen patients (40%) had a complete response, 9 (26%) partial and 12 (34%) no response. In the 23 responding patients, mean duration of response was 6 months. In 17 patients the response was present until death. There was no significant relationship between pain response and patients' age or type of primary cancer. No side effects were recorded other than mild and temporary drop in white blood cell and platelet counts. Three patients with a complete response had a second injection of Sr-89 after progression of pain. One of these patients had a second partial response; the other 2 did not show a response to the second injection. The use of Sr-89 for treatment of widespread painful bone metastases from prostate and breast cancers in our department showed a 66% rate of response and a mean response duration of 6 months, with no significant side effects.

The basic question of threshold for the ablation of thyroid remnant after surgery remains unanswered. However, radioiodine therapy is still being used as a standard method of treatment.In present investigation treatment responses of 100 patients with

131thyroid cancer treated with 3600 MBq of I is studied. Response

054-IRAStrontium-89 in Palliative Treatment of Widespread Painful Bone Metastases: Response Rate and DurationPeiman Haddad MD, Farhad Ghadiri MDRadiation Oncology Department, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran

055-IRAStudy of ablation efficiency of 3600 MBq of I-131 in the Treatment of Thyroid CarcinomaTakavar A, Eftekhari M, Fard-Esfahani A, Beiki D Research Institute for Nuclear Medicine, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

to treatment of 100 patients (33 males and 67 females) was evaluated by serum TSH, Tg levels and areas of thyroid remnant as

131measured by whole body scan with I performed 6 months after therapy. Treatment response was evident by decreased or lack of 131I uptake in the thyroid bed and Tg 5 ng/ml. Remnant area was decreased about 74.5% in females and 75.5% in males. No significant difference between sex groups was observed. Because of radiation protection concerns and socioeconomic reasons,

131lower ablations doses of I ( 1110 MBq) might be as effective, and should be evaluated.

186 185 186Feasibility of Re production has been studied by Re (n, ) Re reaction in a Research reactor,. Liquid Scintillation Counter has

186measured the activity of Re-perrhenate about 7.2 mCi/mg at 5 days after end of irradiation. To determine the required specific

186activity and possibility of application of Re liquid for intravascular brachytherapy calculation of dose distribution has been carried out using MCNP-4b code of Monte Carlo . Depth dose rate in 0.5 mm depth of around angioplasty balloon (20mm length, 3mm diameter) has been calculated that it is 1.152 [(cGy/min) (mCi/ml)]. Suitable specific activity for delivery of /

doses from 12 to 20 Gy in 4min has been determined, 300 to 400 (mCi/ml). Eighty-two percent of the energy deposited in the first 0.5mm of vessel wall from the balloon. Therefore there is a little

90non-uniformity in respect to other beta emitter as such as, Y and 188 188W/ Re. Medical internal radiation dosimetry (MIRD) was calculated assuming that contents had been released into the

186system circulation. Re DTPA accommodate only kidneys and bladder specifically, there fore radiation dose of whole body is less

99m 186than Tc-DTPA. We conclude that production of Re DTPA

185easy by irradiation of enriched Re target in a 5MW Research Reactor and also 186Re-DTPA is safe to use and suitable for intra-vascular brachytherapy for coronary with centric cross section.

Auger electrons which enter into cells cause biological effects with high-LET short range radiation on the neighborhood. The purpose of this study was to investigate the internalization of In-111-N-myc-AS and suppression of N-MYC in human neuroblastoma cells. Fifteen-mer AS, which was complementary to the region of the mRNA of N-myc beginning with ATG start codon, was derivatized with SCN-Bn-EDTA and labeled with In-111. In-111-N-myc-AS (1.33MBq/nmol) was prepared as naked form and encapsulated in cationic multilamellar liposome (CML).

O56-IRA186Dose Calculations of Re For Production and Feasibility of

use to Intravascular Brachyherapy After Coronary Angioplasty

1 1 2Taghizadeh-asl M , Pourbeigi H , Meigooni AS , Ghahremani 1 1AR , Ghafoorian H

1Department of Nuclear Research Center, Atomic Energy 2Organization of Iran and Department of Radiation Medicines,

University of Kentucky, USA

057-JAPEffect of Auger Electrons Internalized as Indium-111 Labelled N-MYC Phosphorothionate Antisense Oligonucleotide (In-111-N-MYC-AS) on Human Neuroblastoma Cells: In vitro and In vivo studiesWatanabe N, Tanada S, SasakiY.Department of Medical Imaging, National Institute of Radiological Sciences, Chiba 263-8555, Japan

g

S-38



The internalization of In-111-N-myc-AS with or without CML into human neuroblastoma SK-N-DZ cells was determined both in vitro (cell culture) and in vivo (tumor bearing nude mice) studies by Southern blot analysis. Quantity of N-MYC in the tumor cells was also measured by Western blot analysis. In in vitro system 0.69?0.02pmol of In-111-N-myc-AS (80pmol) with CML was internalized in the cells (5X106) by 12h at 4?C, which increased to 8.05?0.43pmol at 37?C. The internalized naked In-111-N-myc-AS was 0.58?0.01pmol and 0.92?0.03pmol at 4 and 37?C, respectively. In vivo study revealed the internalization of In-111-N-myc-AS (8nmol) with CML in tumor cells (5X106) as 6.44?0.71pmol, while none (0pmol) of naked In-111-N-myc-AS was internalized. The effect of Auger electrons was shown by a decrease of N-MYC of the tumor cells by 20.6?2.49% in vitro and 12.9?1.17% in vivo in the case of In-111-N-myc-AS with CML, whereas unlabeled AS with CML or In-111-phosphorothioate sense oligonucleotide did not decrease the quantity of N-MYC of the tumor cells in vitro or in vivo. In conclusion, In-111-N-myc-AS with CML could be internalized into human neuroblastoma cells and suppress the activity of N-myc gene, which may prove useful for targeted Auger electrons radiotherapy.

PET and PET/CT are the fastest growing imaging modalities worldwide. PET technology has already become an important diagnostic tool for staging disease, evaluating the treatment effects and the long-term follow-up of cancer patients in developed nations. In summary, PET/CT studies can affect the patient management in about 25-30% of the oncological patients.The most useful indication of FDG-PET in cancer patients is the differentiation between recurrence and post-therapy changes. Responses to therapy can be identified earlier and with greater accuracy than is possible with anatomic imaging modalities. Prognostic information available through 18F-FDG PET is superior to that of conventional imaging for many cancers. The sensitivity and specificity of FDG-PET in detecting recurrence amounted to 94% and 92% respectively. On the contrary, the sensitivity and specificity of conventional images were only 78% and 68%. FDG-PET is increasingly used to monitor tumor response in patients undergoing chemotherapy, chemo-radiotherapy and radiopharmaceutical therapy. 18F-FDG PET is an accurate study for differentiating residual viable tumor tissue from therapy-induced fibrosis. It may allow the prediction of tumor response and patient outcome very early in the course of therapy. Overall survival and progression-free survival are correlated highly significantly with metabolic responders in PET. In one paper, the median progression-free survival of metabolic non-responders was only 1.8 months but that of metabolic responders was 5.9 months. In patients without a significant change in tumor 18F-FDG uptake, the treatment change should be considered early in the course of therapy.In patients with solid tumors treated by preoperative chemotherapy, a change in 18F-FDG uptake of 35%-50% within the initial weeks of chemotherapy has been found to provide the highest accuracy for the prediction of histopahologically complete response. Early identification of non-responding patients is of great clinical importance. Effective chemotherapy causes a marked decrease in tumor 18F-FDG uptake (15-40%) within 1-3 wk after the initiation of therapy.This has been extensively investigated for malignant lymphomas,

058-KORThe Role of PET in Monitoring Therapeutic ResponseLee MC. Department of Nuclear Medicine, Seoul, Korea

but also for several solid tumors, such as breast cancer. Visual interpretation of PET scans is sufficient for assessment of tumor response after completion of therapy. However, quantitative analysis is generally required, if PET imaging is used to predict tumor response early in the course of therapy.FDG PET may become the method of choice for the early assessment of treatment response to primary chemotherapy in patients with breast cancer. Although about 70-80% of patients show clinical response to primary chemotherapy, the pathological response rate is only in the range of 20-30%. The sensitivity and specificity to predict complete pathologic response after the first course of chemotherapy were 90% and 74%, respectively. Therefore, as early as after the first course of therapy responding and non-responding tumors can be differentiated by PET. One baseline FDG PET and one scan after the first course of primary chemotherapy seems to be sufficient to identify non-responders at an early stage of therapy. By a threshold defined as a decrease below 55%, compared to the baseline scan, all responders were correctly identified after the first course (sensitivity 100%, specificity 85%). FDG PET may be helpful for improving patient management (30-40%) by avoiding ineffective chemotherapy and unnecessary side effects FDG PET can also be useful for prediction of response to hormonal therapy. In one study which investigated biological tumor characteristics like glucose metabolism and perfusion, determined with dynamic FDG PET and 15O-water PET before any therapy concluded that PET could predict the response to neo-adjuvant chemotherapy. The high pretreatment metabolic rate for FDG predicted a poor response to therapy and a low metabolic rate relative to blood flow was found to be a predictor of complete response

I-131 therapy for thyroid cancer and hyperthyroidism is used since 1964 in Latvia, but for patients with euthyroid nodular or diffuse goiter only since 1995.The aim of this study was to analyse 5 year statistics and to inform doctors about possibilities of such therapy method in Latvia. In between 1995-2000 in Latvian Oncology Centre 75 patients with euthyroid goiter were treated with I-131. Radiation dose for thyroid volume was 100-150 Gy. Patients with goiter volume >100 ml and with tracheal compression received radiation dose 50 Gy 2 or 3 times. There were 25 patients with recurrent goiter after surgery, 50 patients has increased surgical risk because of other severe diseases or retrosternal localization of goiter.Our results demonstrated that 6 month after I-131 therapy there was reduction of goiter volume by 20% in 38 cases, by 30% in 19 cases and by 50% in 11 cases. In 7 cases there was no reduction of goiter volume, but the growing of goiter was stopped (follow up 4 years).We conclude that I-131 therapy is effective for reducing of thyroid goiter volume and is used in Latvia (20-25 patients per year). If the aim of I-131 therapy is not only to reduce the hyper function of nodular goiter, but also to reduce the goiter volume, the suppression of TSH is not compulsory.

059-LATI-131 Therapy for Euthyroid Goiter in Latvia.Berzina A, Berzina D, Roznere L, Vevere ILatvian Ocology Centre

S-39



060-LITIs it Worth to Calculate the Dose of Radioiodine?Mikalauskas V1, Kuprionis G1, Vajauskas D21Department of Nuclear Medicine, Kaunas Medical University Hospital, Lithuania and 2Kaunas Medical University, Lithuania

Administration of empirical doses of radioiodine (RAI) has been preferred to calculated doses in many hospitals, because the need to measure the size and the iodine uptake in the thyroid involves considerable inconvenience to the patient and additional costs. The preparation of RAI of varying activities also means extra work. Today there is no general consensus on whether radioiodine should be given as a fixed dose or should be calculated. There is also no consensus regarding the question of which radiation burden should be administered to a given volume of thyroid if the activity is calculated. However, while it is possible to deliver a relatively precise dose of radiation to the thyroid gland, maybe it is worth doing this?The aim of this study was to investigate the results of different uptake and volume dependent target doses on clinical outcome of patients with hyperthyroidism in Graves' disease, multi-nodular toxic goiter or toxic adenoma after radioiodine therapy.We reviewed the records of 428 patients (389 women and 39 men, mean age 56.8±12.9 years) who had received radioiodine treatment for Graves' disease and multinodular toxic goiter (n=312) or toxic adenoma (n=116) during the period of 2000-2004 in Kaunas Medical University Hospital. Most patients were given antithyroid drug therapy in order to achieve euthyroidism before treatment with RAI. Radioiodine uptake test with repeated measurements at 2, 6, 24, 48 and/or 72 and/or 96 hr to define the effective half-life was performed. In addition, all the patients underwent thyroid ultrasonography and scintigraphy to define the volume of the thyroid. The 131I activities were calculated according to the formula of Marinelli. In addition to the normal calculation individual target doses were adjusted to the thyroid volumes of each patient before therapy. For statistical evaluation, the patients were divided into four groups: group I included those with a thyroid volume <15 ml before therapy, group II included those ranging from a 15-25 ml, group III included those ranging from a 26-50 ml and group IV included those with thyroid volumes >51 ml. Statistical analysis was performed using SPSS for Windows, version 12.0. A p-value less than 0.05 was considered statistically significant.The mean effective half-life for thyroid gland in all patient groups was 5.32 days and there was no significant difference between the groups. Patients with Graves' disease and multinodular toxic goiter in group I (n=42) received a target dose of 124.87±15 Gy, in group II (n=77) - 128.35±10 Gy, in group III (n=153) - 124.29±22 Gy. But, the patients in group IV (n=29) received a target dose of only 103.74±35 Gy, because the administered activity of 131I for outpatients is limited to 400 MBq according to the Lithuanian regulations. In subgroup of patients with toxic adenoma an activity was calculated to deliver 140 and 160 Gy for the treatment in group I (n=72) and in group II accordingly. Received target dose in this subset of patients was in group I 156.19±20 Gy and in group II (n=38) - 158.19±22 Gy. Administration of a single dose of RAI resulted in the control of hyperthyroidism in 91.8% of patients. Unfortunately 35 (8.2%) patients with Graves' disease required the second and two of them the third RAI treatment to achieve either a hypothyroid or a euthyroid state. The second target dose was significantly higher (p<0.05) than the first (128±25 Gy vs 119.8±24 Gy) because was adjusted to the significantly reduced (p<0.05) after the first

treatment thyroid volume (40±18 ml vs 18.4±11 ml) and was given for persistent hyperthyroidism after a mean of 13 months (minimum 3 months, maximum 34 months). Not sufficient first target dose was delivered to the thyroid due to Lithuanian regulations as mentioned before. The third treatment of 120 and 142 Gy was given in four and nine months in two cases.We concluded that therapeutic success was associated with calculation of individual target dose adjusted to the thyroid uptake, volume and the cause of hyperthyroidism in each patient.

Cells express a variety of different receptor proteins on their surface, some of which have a high affinity for regulatory peptides, such as somatostatin. Somatostatin receptors (SSTR) are over-expressed in several human tumours, especially those of neuroendocrine origin. The biological effects of SSTR are mediated by five specific receptor subtypes (SSTR 1-5) to which the native peptide binds. However, somatostatin analogues have

major differences in their affinities for different receptor subtypes.DTPA-octreotide binds with reasonably high affinity to SSTR 2 and with low affinity to SSTR 5. RC-160 has enhanced binding affinity to SSTR 4, while depreotide preferentially binds to SSTR 2, 3 and 5. DOTA-lanreotide binds to SSTR 2, 3, 4 and 5 with high

3affinity, and to SSTR 1 with low affinity. DOTA-Tyr -octreotate exhibits the highest affinity for SSTR 2. Somatostatin analogues labelled with a variety of gamma-, positron- and beta-emitters, are becoming of increasing interest in tumour targeting for either the localization or the targeted radiotherapy of neoplasms.

99mThe aim of this study was to evaluate the use of Tc-depreotide in visualisation of neuroendocrine tumours and other tumours

111expressing somatostatin receptors, when In-pentetreotide and/or 123I-MIBG scans were negative or inconclusive and to choose a suitable radiopharmaceutical for targeted therapy.The case records of 23 patients (17 women and 6 men, mean age

99m56.78 range 26-78) who underwent Tc-depreotide scans over the period from January 2004 to March 2005 were reviewed. Fourteen patients presented with neuroendocrine tumours, 2 with Merkel cell tumours, 2 with thymic carcinomas, 3 with medullary and 1 with papillary carcinoma of the thyroid. Two patients had

90 131 153previous Y-DOTA-lanreotide, one I-MIBG and one Sm-EDTMP therapy. Whole body imaging was performed with tomography of the liver at 1 and 4 hours after intravenous injection

99m 111of 700-750 MBq of Tc-depreotide. 21/23 patients had In-pentetreotide whole-body scintigraphy with tomography of the

123upper abdomen. Twelve of these patients also had I-MIBG 18imaging. 2/23 had F-FDG-PET scans which were negative. One

experienced reader reviewed all the scans and compared uptake between the tracers.

99mResults showed that Tc-depreotide imaging demonstrated 111positive findings in 19 cases (82.6%) and was superior to In-

pentetreotide imaging in 15 cases and PET in 2 cases. In 2 cases 111 99m 123In-pentetreotide was better than Tc-depreotide. I-MIBG scintigraphy was positive only in two cases. All three imaging modalities were negative in 2 cases. One patient had two populations of tumour cells, presenting with different pattern of uptake on depreotide, pentetreotide and MIBG scan. According to the intensity of uptake different possible treatments were

90 131recommended: in 5 cases Y-DOTA-lanreotide, in 1 case I-

061-LITSomatostatin Receptor Imaging and Therapy an Ever Expanding ChoiceKulakiene I, Warbey VS, Buscombe JR, Hilson AJW Dept of Nuclear Medicine, Royal Free Hospital, London, UK

S-40




90MIBG and in 1 case intra-arterial treatment with Y-sirspheres for wide spread liver metastases.

99mWe conclude that Tc-depreotide scintigraphy is a very promising method in the visualisation of somatostatin receptor expressing tumours and in patient selection for the targeted therapy, choice of therapy and method of administration.

Eighty two patients with painful skeletal metastases of malignant diseases (predominantly prostate) were treated with strontium-89 in Oncoradiotherapy department of Vilnius University Institute of Oncology during 2000-2004 period. The patients received strontium-89 chloride (Metastron, Amersham Health) at a dose of 150 MBq intravenously. Pain palliation was evaluated on the basis of increase in the Karnofsky performance status, the pain and narcotic test improvement at 3 months. The efficacy of strontium-89 treatment was graded as good, partial or absent.The response was good in 52 (63%), partial in 20 (24%), and there was no response in the remaining 10 (12%) of cases. A complete improvement was observed in 13 (16%) patients. Duration of the response ranged from 2 to 7 months (mean 3 months). During a 3-year study, strontium-89 treatment was successively repeated up to 4 times in some patients who benefited from the first strontium-89 administration and did not show signs of myelosuppression. After repeated treatment, relief was consistent and the effectiveness was as good as after the first dose of strontium-89. During the course of strontium-89 treatments, transient signs of myelosuppression were observed , with a partial or full recovery within 5 months.In conclusion, palliative treatment with strontium-89 improves the quality of life in most patients suffering from painful skeletal metastases. If necessary, the treatment may be repeated safely and with the same efficacy as is achieved after the first dose.

Radio Iodine (RI) therapy is preceded by anti thyroid drug treatment in most centres. There is a general notion that this is a pre requisite for RI therapy. There have been some sporadic reports in the past emphasizing that euthyroid state is not necessary in all cases before RI. However, no prospective randomized study has been reported in recent literature. The aim of this prospective study was to find out whether prior treatment with anti thyroid drugs showed any advantage in comparison to direct application of radio iodine in hyperthyroid patients. Seventy-two clinically and bio chemically proven cases of hyperthyroidism were randomized into two groups , each with 36 patients. They were matched by age, sex and size of goiter. After establishment of the diagnosis the patients were either subjected to anti thyroid drug treatment (Group A) or given calculated dose of radio iodine (Group B). After being euthyroid for at least 4 weeks the Group A patients were asked to stop the drugs (Neomercazole) for 3-5 days and radio iodine was administered. Patients in both

062-LITBone Pain Palliation with Strontium-89 in Cancer Patients With Bone MetastasesS.Tiskevicius¹, Z.Baranauskas², A.Burneckis², E.Aleknavicius²¹Vilnius University Institute of Oncology, Nuclear Medicine Department and ²Vilnius University Institute of Oncology, Oncoradiotherapy Department, Lithuania

063-MALRole of Antithyroid Drug Treatment Prior to Radioiodine Therapy in HyperthyroidismDas BK*, Pradhan PK, Senthilnathan MS, Malhotra GSanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, INDIA (* Presently Visiting Professor, Universiti Sains Malaysia)

groups were prescribed beta blockers for 4-6 weeks. Average radio iodine dose in both groups was 5 ± 0.92 mCi. All patients were evaluated both clinically and bio chemically 3, 6, 12 months after the radio iodine application. The duration to achieve euthyroid state, patient tolerance and side effects if any were meticulously recorded.In the pre treated group 72.1, 83.4 and 97.2 % of the patients

Since 1997, radioactive iodine (I-131) has become the most widely used therapy for patients with hyperthyroidism cased by Graves' disease in the Mongolia. Our seven years clinical experience was reviewed to evaluate the efficacy of the therapy. We treated 150 patients (119 female and 31 male) with hyperthyroidism with I-131 (mean dose 8.2 mCi) between 1997 and 2004. The dose calculation was based on 24 hours thyroid uptake, thyroid galnd size and degree of toxicity. We determined their thyroid status after 1 year in relation to age, pretreatment with an antithyroid drug, pretreatment thyroid size and whether or not there are thyroid nodules.Out of the 150 patients, 87(58%) were euthyroid, 30 (20%) hypothyroid at 1 year after treatment, and 33 patients (22%) had persistent hyperthyroidism and required second treatment. The patients who had persistent hyperthyroidism were younger in age, had larger thyroid glands, some of them had thyroid nodules and 27 patients (81%) pretreatment with anti-thyriod drugs for more than 6 months.Our results showed that the majority of patients with Graves' hyperthyroidism had a effective treatment. However, 22% of patients with younger age, larger thyroid glands, patients with thyroid nodules and who had anti-thyroid drugs for more than 6 months had undergone repeated treatment. A higther dose of I-131 maybe advisible in such patients. In order to establish correct treatment dose we may need more precise dosimetry study.

attained euthyroid state at 3, 6, 12 months respectively. Five patients needed a second dose after 3 months. No side effect or complications were observed. In group B 77.7, 88.8 and 94.4 % of patients achieved euthyroid status at 3, 6 and 12 months respectively. There was no side effects or complications noted. However, 16.7 and 22.2 % of the patients in group A and 27.7 and 36.1 % of the group B became hypothyroid at 6 and 12 months respectively. They were treated with Thyroxine supplementation. Overall there was no significant difference in the outcome of the therapy in both groups (p >0.05).We concluded that it is not necessary to bring hyperthyroid patients to euthyroid state with anti thyroid drugs before administering radio iodine. Radio iodine can be considered as a definitive, effective and safe initial therapy in hyperthyroidism. Only in sever cases of thyrotoxicosis pre treatment may be necessary before subjecting to radio iodine application.

064-MONIodine-131 Therapy for the Treatment of HyperthyroidismEnkhtuya B, Tsevelmaa L, Erdenechimeg SDepartment of Nuclear Medicine, First State Central Hospital of National Medical University, Mongolia

065-MONTreatment of HCC with Re-188 lipiodol Initial Experience in Mongolia

1 1 2 3Erdenechimeg S , Onkhuudai P , Gonchigsuren D , Sundram FX , 4 5Divgi C , Padhy A.K

1 2Department of Nuclear Medicine; Department of Radiology, First State Central Hospital of National Medical University,

S-41


3 Mongolia; Department of Nuclear Medicine, Singapore General 4 5Hospital, Singapore; MSKCC, New York, USA and Gujarat

Cancer & Research Institute, Ahmedabad, India

066-MON188Radiation Synovectomy With re-tin Colloid in Histological

Study1 1 2Erdenechimeg S , Tsevelmaa L , Bayarmaa B

1Department of Nuclear Medicine of First State Central Hospital, 2Mongolia and Department of Pathology, Health Science Medical

University, Mongolia

The aim of this study was to assess the safety and efficacy, in patients with inoperable hepatocellular carcinoma (IHCC) of

188intra-arterial Re-lipiodol given at an amount of radioactivity calculated to deliver acceptable radiation absorbed doses to critical normal organs (liver, lung and bone marrow). Rhenium-188 was eluted from a tungsten/rhenium generator

188system from ORNL. Conjugation of Re to lipiodol was carried out using a HDD kit from Korea. Both were provided through the IAEA. Thirty nine patients with HCC were studied. Patients had acceptable hematopoietic and hepatic parameters at baseline. All patients had measurable disease on CT. A transmission whole body scan was carried out on the morning of the study. A “scout”

188activity 207 ± 57 MBq of Re-lipiodol was administered into the relevant hepatic arterial tree accessed in the interventional suite, and static images were obtained in Nuclear Medicine to provide quantitative images of the liver (including tumor), lungs and whole body. The maximum tolerated activity (MTA) was defined as that which would deliver no more than 30 Gy to liver, 12 Gy to lungs or 1.5 Gy to red marrow, calculated using a MIRD-based spreadsheet developed at MSKCC, New York, USA. An amount

188of Re-lipiodol not more than the MTA was then administered under identical conditions. Patients were followed for toxicity and efficacy until death or disease progression. Twenty one patients were treated twice, and two patient three times.The therapy was well tolerated with no major side-effects observed. Logistic and other constraints prevented delivery of the MTA in all patients, with 35.5% (1.33-2.7GBq) of MTA being administered. Despite this, 16.6% had major (PR+CR) response and 56.6% had stabilization of disease. Quality of life was improved in 12/39 patients, with a median overall survival of 14 (4-24) months and a median progression-free survival of 9 months.

188We conclude that intra-arterial therapy with Re-lipiodol is feasible in Mongolia. The therapy is safe and preliminary efficacy results are encouraging. The inability to treat at MTA suggests that other methods, including multiple treatments cumulatively less than MTA, may be considered. The study is ongoing, as is analysis of tumor radiation absorbed dose and treatment efficacy.

Radiation Synovectomy has been widely used treatment modality 188of chronic inflammatory joint diseases in many countries. Re-tin

colloid is a relatively new radiopharmaceutical agent, which efficacy and safety were reported and it appears feasible to use in Mongolia. The aim of our study is to generate antigen-induced arthritis model in the rabbits knee, conduct radiation synovectomy

188with Re-tin colloid and demonstrate treatment efficacy by histological changes. Six male white rabbits (2-2.5 kg) were used in this study. To produce antigen-induced arthritis model 0.5 ml of Freund's complete adjuvant was administered twice within two weeks by intra-articular injection. To complete inflammatory

changes histological examination was done in two rabbits. The synovial membrane showed round cell infiltrates with neutrophiles, leukocytes plasmocytes and histocytes. In addition, there is noted capillary hyperemia. Each rabbits received 37 MBq of 188Re-tin colloid. The animals were sacrificed at 1 and 4 weeks after injection and knee joints dissected and sectioned for

188histological study. Within one week after injection of Re-tin colloid into the knee joints, the synovial membrane showed round cell infiltrates consisting of lymphocytes, histocytes, fibrocytes and deposits of fibrin. After 4 weeks, the inflammatory changes almost disappeared and there was fibrotic changes and epithelization of synovial membrane. There was no damage of articular cartilage in any histological study. We find good

188hystological response of Re-tin colloid radiosynovectomy in inflammatory joint diseases.

Specific targeting of neuroendocrine tumours for therapy may be achieved either via the metabolic route (MIBG), via receptor binding (peptides) or via the immunological route (antibodies). Any malignant neural crest tumour, showing sufficient uptake and

131retention of I-meta-iodobenzylguanidine (MIBG) on a diagnostic tracer study is a candidate for therapy using this agent.

131The principle indications for I-MIBG therapy are malignant pheochromocytoma and paraganglioma, neuroblastoma stage III and IV, medullary thyroid carcinoma and symptomatic, metastatic carcinoid tumors.

131At an EANM Radionuclide Therapy Committee workshop on I-MIBG therapy in 1999 the results of treatment in 534 patients with neural crest tumours were gathered, showing cumulative objective response rates of 51% for malignant pheochromocytoma, 48% for paraganglioma, 51% for neuroblastoma, 23% for medullary thyroid carcinoma and 8% for carcinoid tumors. Moreover, symptomatic palliation occurred in more than 60% of the patients. These results compare favorably with the best reported results of combination chemotherapy.An active uptake-1 mechanism at the cell membrane and neurosecretory storage granules in the cytoplasm of neural crest

131tumours are responsible for the uptake and retention of I-MIBG, respectively, resulting in high tumour/nontumour ratio's. Many drugs are known or may be expected to interfere with (i.e. have a

131negatively effect on) the uptake and/or retention of I-MIBG by the tumour cell. In contrast, there are also factors which may

131influence either the uptake/retention of I-MIBG or the results of therapy in a positive way. Possible interventions:

125 2111. Use of other labels, for example I-MIBG, At-MABG and 76Br-MBBG, which, in view of their ultrashort pathway, may have a role in the treatment of micrometastases and bone marrow

131in?ltration, particularly as the results of I-MIBG therapy under these circumstances are poor.2. By increasing the specific activity and the production of non-

131carrier-added I-MIBG tumour uptake may be improved, although. the optimal speci?c activity may vary with the tumour type.3. Prolonging retention, e.g. by calcium channel antagonists. Blake et al. showed that Nifedipine (Adalat) altered the kinetics of 131I-MIBG therapy in some patients: the observed increased uptake

067-NET131Interventions in I-MIBG Treatment of Neuroendocrine

TumoursHoefnagel CA, The Netherlands Cancer Institute, Amsterdam

S-42



and retention led to a higher absorbed radiation dose to the tumour. 4. Alternative routes of administration may enhance the tumour uptake, for instance via the intra-arterial or intraperitoneal route. When the metastases of a neural crest tumour are confined to the

131liver, administration of I-MIBG therapy via hepatic arterial catheter is feasible. 5. Combination with other treatment modalities, e.g. chemotherapy and/or total body irradiation, myeloablative chemotherapy requiring autologous bone marrow or stem-cell

131rescue, accepting additional toxicity. In neuroblastoma I-MIBG therapy has been combined with oxygen treatment under hyperbaric conditions and high doses vitamine C, resulting in the formation of hydroxyl radicals, which are toxic to the

131neuroblastoma cell on top of the I-MIBG radiation effect to which it is exposed.

1316. Changing the order of treatments: I-MIBG therapy as the initial therapy instead of preoperative combination chemotherapy in children presenting with advanced disease/inoperable neuroblastoma. Initial results have demonstrated the feasibility

131and effectiveness of upfront I-MIBG therapy: a higher objective response rate (>70%) and considerably less toxicity compared to 131I-MIBG therapy after conventional treatment. 7. Prevention of tumour cell repair: in high risk neuroblastoma

131(stage IV, >1 year of age), upfront I-MIBG therapy has been combined with Topotecan, a topoisomerase I inhibitor, which may enhance the radiation induced cytotoxicity by interfering with repair of damaged cells.8. Combining radionuclide targeting mechanisms: as in nude mice with SK-N-SH neuroblastoma xenografts the therapeutic efficacy

131of I-labelled anti-L1-CAM antibody chCE7 in comparison with 131I-MIBG and in patients the complementarity of these agents in targeting neuroblastoma was demonstrated, combined or alternating MIBG- and radioimmunotherapy may be a future approach. 9. Induction of tumour cell differentiation, e.g. using retinoic acid or interferon, may increase the speci?c uptake and retention of 131 I-MIBG in tumours. The successful transfection of thenoradrenalin transporter gene (NAT) into NAT negative neuroblastoma cell lines offers another possibility to improve the efficacy of MIBG therapy.10. Blocking extratumoural specific uptake by unlabelled (“cold”) MIBG. In nude mice with PC-12 pheochromocytoma xenografts excess unlabelled MIBG leads to significant reduction of tumour

125uptake of I-MIBG, but in patients with carcinoid tumors treated with unlabelled MIBG favourable changes in the biodistribution

131of I-MIBG were observed, increasing the tumour/non-tumour ratio by a factor 1.1-2.1 in 70% of the patients. Combined therapy

131of high dose unlabelled MIBG followed by 7.4 GBq I-MIBG may result in a greater biochemical response and palliative effect than each of the treatments alone.

131I conclude that I-MIBG therapy is effective in several neural crest tumours, attaining 50% objective response in pheochromocytoma, paraganglioma and neuroblastoma and providing excellent palliation to most patients. The tumour targeting and therapy effectiveness may be enhanced by pharmacological interventions and by combination with other treatment modalities.

068-PAKFormulation and evaluation of Beta-emitting Radionuclide Labeled EDTMP for Bone Pain PalliationSohaib M, Mushtaq A, Jehangir M, Yousuf M, Azra P

Department of Medical Sciences, PIEAS & Isotope Production Division, PINSTECH, Islamabad, Pakistan

069-PAKTrans-Arterial Radioconjugate Radionuclide Therapy For Hepatocellular Carcinoma; Feasibility & Applications In PakistanAsghar SINMOL, Lahore, Pakistan

070-PERImpact of Educational Strategies in Positioning Samarium-153 EDTMP as a Treatment for Metastatic Bone PainSeminario C, Morales R, Castro M, Cano RA, Mendoza GCenter of Nuclear Medicine (Instituto Peruano de Energía Nuclear) IPEN-INEN

In a quest for more effective radiopharmaceutical for palliation of pain experienced by metastatic cancer patients, this study relates the results obtained with therapeutic beta emitter radionuclides of Samarium-153, Holmium-166, Yttrium-90 and Lutetium-177 complexed to bone seeking phosphonate ligand of ethylenediamine tetramethylene phosphonic acid (EDTMP). The objective of this study is to formulate and evaluate Samarium-153, Holmium-166, Yttrium-90 and Lutetium-177 labeled EDTMP for

153bone pain palliation and to compare them with Sm-EDTMP that is currently being used in many centers of the world. All the radionuclides were prepared by n,ã reaction. Quality control was checked by paper chromatography and paper electrophoresis. Various parameters were optimized to formulate these radiopharmaceuticals with maximum labeling efficiency. Sprague-Dawley male rats were used for biodistribution and

153imaging study. The labeling efficiency of Sm-EDTMP was found to be > 99% at pH 7.5 with 1:5 (Sm: EDTMP) molar ratio

90incubated for 20 minutes at room temperature. For Y-EDTMP the labeling efficiency was > 95 at pH 7.5 with ligand: molar ratio

166from 5-12. Ho-EDTMP showed that the complex can be prepared with radiochemical purity of >95% using ligand: molar

177ratio from 8-12 at pH 7.5. Lu-EDTMP complex showed labeling efficiency >95% using ligand: molar ratio from 20-30 at pH 7.5. During bio-distribution study, skeletal uptake was found to be

177 153maximum for Lu-EDTMP (70±2.4%), followed by Sm-90 166EDTMP (58.5±2.8%), Y-EDTMP (45±2.1%) and Ho-EDTMP

(36±2.1%). All these radiopharmaceuticals showed good renal and rapid blood clearance. The biodistribution study of free radionuclides showed significant uptake of activity by soft tissues including lungs, liver and spleen, with minimal uptake in the

153 90skeletal system ( SmCl : 7.5±0.04%, YCl : 1.75±0.6%, 3 3

166 177HoCl : 3.3±0.3%, LuCl : 2.5±0.1%). Imaging study carried 3 3

153 177 166out for Sm-EDTMP, Lu-EDTMP and Ho-EDTMP showed good uptake of activity by the skeletal system (including epiphyses, spine and facial bones). Therefore, it was concluded that labeled complexes of these lanthides can be used effectively in the therapy for bone pain

177palliation, Lu-EDTMP have more potential in this regard. Chlorides of the lanthides cannot be used for bone pain palliation due to their poor skeletal localization.


To educate is a difficult task but its results make efforts worthwhile. Many patients in Peru suffer from intractable bone

S-43



pain due to metastases. Since 1993 radionuclides were used to palliate bone pain due to metastases in Peru. First, with the help of the IAEA, Peru participated in a clinical trial using Phosphorus 32 and Strontium 89. Then, efforts were performed to produce Samarium 153 EDMTP locally, which was achieved in 1995. Nevertheless, years passed and Samarium use did not increase proportionally to the needs of people with cancer and bone pain, mainly the poor. Educational strategies have been proven useful for delivering solutions to many health problems in other diseases and also in cancer. Health education makes patients and their relatives assume responsible care of their problems. The purpose of this work was to increase Samarium EDTMP use as palliative treatment in patients with bone pain due to metastases, using educational strategies as means to change attitudes towards this health problem.In September 2003, a task group conducted studies in order to apply several methods to achieve the goal of increasing Samarium EDTMP use. Educational strategies employed were performed to provide verbal and written information to patients, physicians, medical students, residents, pain specialists, oncologists and neurologists, as well as general public. Verbal information included radio interviews, television spots and a phone number (in charge of two secretaries, prepared for answering and if not possible, a physician was in charge of attending patient consultation), email and a web page for consultation. Written material was delivered to several newspapers, including clinical use of Samarium, possibilities of being elected for treatment, benefits and risks and a photography of the product. Politics of the institution producing Samarium changed, in order to achieve minimum cost of the product and it was delivered to all publics at the lowest cost for a year, which has finished in December 2004. Three television spots were delivered to public: “Hello, Doctor”, which has a morning audience and in two interviews in news programs, with high rating performance. Five interviews were given in radio programs, one of them was for a feminine audience, three for general public and the other two with national impact. In every program a web page, an email and a telephone number were given for consultation. In Nuclear Medicine Centers in Lima telephone calls have been received since the beginning of the campaign every day, up to date. In a year, a monthly conference

was delivered to physicians. Samarium EDTMP treatment increased substantially after the campaign (Figure1)The more significant means in mass media for changing management were patient education, continuous meetings with specialists and one of the television spots used (“Hello, doctor”), which continues to be delivered in the closed circuit TV network of the social security system. We conclude that repetitive educational strategies have a positive impact in delivering radiopharmaceuticals for bone pain palliation to patients with bone metastases

071-PERInfluence of T-3 produced by Metastatic Thyroid tissue on Iodine-131 Treatment Outcome

1 1 1 1 1Mendoza G , Cano RA , Morales R , Martínez F , Saavedra P , 1 2 2 2 2Vílchez C , Postigo J , Sánchez P , Salas A , Torres F

1Center of Nuclear Medicine (Instituto Peruano de Energía 2Nuclear) IPEN-INEN and 2Head and Neck Cancer Department,

Instituto Especializado de Enfermedades Neoplásicas (INEN)

072-PHITherapeutic Options in the Management of Autonomously Functioning Thyroid AdenomasBarrenechea EA, Ong A Veterans Memorial Medical Center and St Lukes Medical Center, Manila, Philippines

Iodine 131 is currently used as adjuvant therapy for patients with differentiated thyroid cancer since 1960, although influence of this treatment on survival of some patients remains controversial. Different approaches have been taken to select which patients will really benefit from iodine 131 treatment. There are some reports stating that TSH stimulation is not vital to select patients for ablation or treatment with iodine 131. The objective of this study is to determine if the production of T3 by metastatic thyroid tissue has any influence on iodine 131 treatment outcome.Nineteen patients with differentiated thyroid cancer who had been treated with total thyroidectomy and had received at least one dose of ablative treatment with iodine 131 were studied. Hormone replacement treatment with T4 was withdrawn in these patients, for one month. All patients had a whole body scan after iodine 131 therapy. TSH, fT4 and T3 were determined by RIA after withdrawal of treatment with T4. Patients were divided in two groups: One group had T3 < 60 ng/100 ml and the other one, T3 > 60 ng/ml. Tg was measured in both groups before and after treatment with iodine 131. A positive outcome was defined when Tg < 5 ng/ml and/or a negative whole body scan. Persistent disease was considered if Tg was > 5 ng/ml, had no change or increased, or if the whole body scan remained positive. Thirteen patients had T3 < 60 ng/100 ml (median = 35,0 ng/100ml, range = 11,3-57,5) and six had T3 > 60ng/100ml (median = 82,9 ng/100 ml, range = 65,6-132,0 ). Outcome after further treatment with iodine 131 in both groups is shown in Table 1.

Considering necessary to select patients for improving outcome of treatment with iodine 131 in thyroid cancer patients, the results of the present investigation show that there is a tendency towards non responsiveness in patients producing T3 in metastatic thyroid tissue. Further studies with a greater number of patients and longer follow-up are necessary to arrive to some conclusions and possible management of these cases.

Autonomously functioning thyroid nodules or adenomas (AFTN or AFTA) was established as a clinical entity in 1918 by Goetsch correlating cellular mitochondrial content with nodular function and showing the inverse correlation between AFTN function and extra nodular tissue function. They are almost always benign and

T3 Response to No response Total

(ng/100 ml) treatment Tg > 5 ng/ml Tg < 5 ng/ml

< 60 5 8 13

> 60 1 5 6

Total 6 13 19

Table 1 Influence of T-3 produced by Metastatic Thyroid tissue onIodine-131 Treatment Outcome

Figure 1 Sale of Samarium increased as a result of end-user awareness

S-44



degeneration, which is common in AFTN, can result in the development of hyperthyroidism. It is therefore important to know the function of these nodules by requesting for the thyroid function tests namely T3, T4, and TSH. They are diagnosed by thyroid scans using I-131 or Tc 99m as a hot solitary nodule in one lobe with the other lobe not appearing on scan or suppressed. The frequency of AFTA worldwide is quite variable depending on geography. It ranges from 1% in North America to 10 % in some areas in Europe and Asia or in areas of iodine deficiency. The traditional methods of treatment of these nodules have been surgery and radioactive iodine ablation. Surgical treatment as a rule is indicated in young patients with nodules larger than 3 cm and those with local compressive symptoms. RAI is used in elderly patients and those who are poor surgical risks. The usual dose ranges from 20 to 30 mCi and is definitely larger that when treating Graves' disease. Others have resorted to PEI or percutaneous ethanol injection with reported success. There has been no definite management of these AFTA due to the variable natural history and some would only recommend observation for asymptomatic small adenomas, which are euthyroid. Therefore this paper studied the results of treatment using RAI ablation, surgery or plain observation for AFTA. Percutaneous ethanol injection is not being done in our center. In the local setting, where thyroid disease is still endemic, the incidence of AFTA is not so high. Graves' disease is still the predominating cause of hyperthyroidism followed by multinodular goiter. Toxic AFTA occurs in 3% of the total hyperthyroid patients. In a ten-year review of the course of the disease after treatment with any of the three modalities of surgery, RAI and purely observation, there still seem to be no common consensus, which the best treatment modality is. Forty-eight patients were included in the study. Among these patients were 43 females and 5 males. Majority were over fifty years old. Among the 48 patients, thirty-nine were toxic and 9 were non-toxic. Of the toxic patients, twelve patients underwent surgery of the affected lobe, undergoing lobectomy or nodulectomy, while 19 patients were given radioactive iodine with a dose range of 20 to 30 mCi. Eight patients just had antithyroid drugs and were just observed. Among the nine patients who were euthyroid, five were just observed but requiring periodic follow-up while four underwent surgery. Two of the total population, one hyperthyroid and one euthyroid patient while being observed after 6 months and three months respectively developed rapid growth of the nodules. FNAB was done which showed well differentiated CA (papillary and follicular) hence underwent total thyroidectomy or near total thyroidectomy, RAI ablation and lifetime thyroid hormone suppression. The results of the 3 modalities were compared and the best results were seen in the group given RAI in terms of cost effectiveness, diminished size of the nodules to disappearance of nodules and relief of symptoms. Hypothyroidism was not a problem as only two patients developed such. Those who were observed only still had the nodules, which became bigger in size with the antithyroids while the incidence of hypothyroidism secondary to surgery was higher in this study as seen in 4 patients. In conclusion, the three modes of treatment has its own weaknesses and strengths and treatment should be individualized depending on which age group the patient belongs (very important consideration) as well as patients choice, size of the nodule and function of the nodule. I-131 may still be the treatment of choice especially in the elderly since they have concomitant cardiac problems. However in the younger age group and for bigger nodules, surgery may be preferred for aesthetic reasons and since they are good surgical risks. Pure antithyroid treatment usually is not recommended.

073-PHIThe Value of PET in DTC with Negative WBS but with Elevated Thyroglobulin levelsBarrenechea EA, Ong A, Santiago JDepartment of Nuclear Medicine, St Lukes Medical Center, Quezon City, Philippines

074-PHIC o m p a r a t i v e E v a l u a t i o n O f T h e E f f i c a c y O f Radiosynovectomy With Conventional Intra-articular Therapy In Rheumatoid Arthritis And Haemophilic Arthropathy (CERAHA)Barrenechea EA, Navarra S, Chua, M.Dept of Nuclear Medicine, St. Lukes Medical Center, Quezon City, Philippines

The ability to detect and treat thyroid cancer early is critically important as most differentiated thyroid cancers (DTC) have very good prognosis. There are, however certain varieties that are quite aggressive and these are usually the ones with elevated thyroglobulin but with negative I-131 whole body scans. These DTC usually transform over time and de-differentiate and lose some or all of their ability to absorb radioactive iodine. These cells may, however still be able to absorb FDG (used in PET scan) which could suggest thyroid cancer cells. This study was conducted in patients with DTC namely papillary and follicular with negative whole body scans using I-131 but with elevated serum thyroglobulin levels of over 10ng/dl. These patients have undergone total thyroidectomy or NTT and I-131 therapy. This was done to determine the usefulness and value of the FDG PET for thyroid cancer cases.There were 15 patients in all, with 11 females and 4 males. Age range was 17 to 78 years old. Fourteen cases had papillary thyroid cancer and one had follicular type. Of the 15 patients, eleven (11) had negative whole body scans using 5mCi of I-131 with elevated serum thyroglobulin levels ranging from over 10 ng/dl to 311.12ng/dl .All these patients underwent PET scans and showed positive results. The other four patients had faint tracer uptake by I-131 WBS and showed positive PET results with additional sites of metastases.We conclude that FDG PET scan is a sensitive tool to detect radioiodine-negative recurrence and metastases in patients with elevated serum thyroglobulin levels among thyroid cancer patients. The value of PET lies in the fact that it can impact or change the treatment and early diagnosis of thyroid cancer can be made.

The objective of this study is to determine the therapeutic efficacy of radiosynovectomy on rheumatoid and hemophilic arthropathy as compared to the usual intra-articular steroids on painful joints. Rheumatoid arthritis is a chronic, systemic and inflammatory disease that involves the joints and is quite disabling. It has a worldwide prevalence of 1%. Hemophilia is a congenital blood disease that produces abnormal bleeding at the musculoskeletal level. It is a sex-linked trait that cause coagulation defects brought about by lack of Factor Vlll for Hemophilia A and Factor lX for Hemophilia B. In this study, under the auspices of IAEA, we used Yttrium 90 colloids and Rhenium 188 intra-articularly in the knee in the experimental group and steroids on the control group. Radioactive colloids (beta radiation) create fibrosis of the hypertrophic and highly vascularized synovium. It leads to coagulation necrosis and sloughing of the cells, destroying diseased pannus and inflamed synovium with the hope that the

S-45



regenerating synovium, after destruction, will be free of the disease. Included in this study were established cases of RA set by the American Rheumatoid Assn which are stage 1, 2, and 3 by Larsen classification, no ankylosis, non-responders for NSAIDS and DMARDS for at least 6 months and with their informed consent. For the hemophilic group, they should have at least 3 bleeding episodes for the last six months and at least with 30% coagulopathy at the time of the procedure. Exclusion criteria included being pregnant or lactating, with infection on site of injection, beyond stage 3 and presence Baker's cyst. Baseline radiography and two-phase bone scans were taken as well as repeating these procedures at 6 an 12 months post-treatment. There were 39 evaluable patients under the experimental group consisting of 18 RA patients (mostly females) and 21 HA patients (all males). Thirty-eight patients were given Yttrium-90 colloid with doses ranging from 60 Mbq to 185 Mbq depending on the age of the patients and one patient was given Rhenium 188 colloid. Fifteen patients were included in the control group where intraarticular Triamcinolone was given at 10 mgs dose. The results of this study is very encouraging with regards the experimental group. Clinical improvement was very evident in most of the cases. These are based on the pain scoring system based on the visual analog scale, lesser requirement for drugs, diminution of swelling, ability to ambulate, better quality of life, deformity and lesser episodes of bleeding and hence lesser or no need for Factor VIII transfusion. In most of the hemophiliacs there were no more episodes of bleeding, and marked improvement on bone scans. Pain at baseline was more common for the RA patients. Improvement was most evident in the hemophilic group consisting of no further bleeding episodes especially after a month of the therapy and if there were any episodes of bleeding, most hemophiliacs did not require Factor VIII replacement. Their quality of life also improved having fewer absences in school and work. Of course objective findings as x-ray and bone scan also showed marked improvement in the HA group while in the RA group some patients (2) remain unchanged on repeat scintigraphy. For the RA group, there was also marked improvement but it was also dependent of the stage when they got into the study. Those on Larsen Stage 1 and 2 responded quite well while those with beginning on Larsen 3 scores responded partially. In the control group under steroids, most of the patients had immediate improvement but the pain relief and swelling only lasted for one to two months wherein by this time the DMARDS and oral steroids and NSAIDS take over. Side effects noted after the procedure were initial flare in 4 cases, fever in 2 patients, and a minor skin discoloration in one patient. In conclusion, radiosynovectomy is a minor intervention, cost-effective and can be done on an outpatient basis. It is effective in those refractory to medical therapy and those not suited for surgery as in haemophilics.

The study was done under the auspices of the IAEA to evaluate the efficacy of low dose (50-60mCi) vs. High dose (100 mCi) for the post-operative remnant ablation of differentiated thyroid cancer and to determine other factors associated with successful ablation. There were eighty-six patients included in the study with a

075-PHIProspective Randomized Trial for the Evaluation of the Efficacy of Low Vs. High Dose I-131 for Post Operative Remnant Ablation in Differentiated Thyroid CancerBarrenechea EA, Laureta EG, Gaston JC, Al-Nahhas A, Padhy AKNuclear Medicine Dept., Veterans Memorial Medical Center and St Lukes Medical Center, Quezon City, Philippines

diagnosis of papillary, follicular or mixed type of thyroid cancer. They all have undergone near total thyroidectomy or total thyroidectomy and without any evidence of metastatic disease. Four to six weeks after the surgery and without thyroid hormone maintenance as well as iodine free diet and drugs, they underwent a total body scan and uptake using 1-3 mci of I-131. Serum TSH and thyroglobulin were also taken. Randomization was made thru the IAEA and the patients either got a low dose or a high dose depending on such randomization. Of the 86 patients included, there were a total of 76 evaluable cases. There were three dropouts because of other medical conditions as upper GI bleeding, lung cancer and leg fracture. The 7 other patients have not completed their follow-up body scan. Among these patients were 67 females and 19 males whose age range was 19 to 84 years old. There were 65 cases with histologic type of papillary cancer, 15 follicular and 6 mixed varieties. Forty-one patients were randomized to the high dose group while 35 patients were assigned to the low dose therapy group. These patients were confined till their radiation activity was below 2mR/hr. Monitoring of the patients were done during their hospital stay. Post-therapy body scan was done but not with all patients. Most of the side effects noted were sialitis, mild neck pains, nausea and occasional vomiting as well as ageusia. These patients were maintained on thyroid hormone depending on their sensitivity but almost all were given 200-300mgs per day. The older patients tolerated only around 150mcgs/day. After four to six months, serum TSH, thyroglobulin and total body scan were repeated. Successful ablation means there are no residual tissues in the neck or an uptake of less than 0.2% as well as a low thyroglobulin of at least less than ten.

Success rate of ablation in low dose vs. high dose of I-131The success rate for ablating residual thyroid remnants in the neck is more evident in the high dose group (100mCi), p= 0.027 as compared to the low dose (50mCi) group, p= 1.000. All patient characteristics were not significantly different from the two randomized groups. Factors affecting success or failure of ablation could be the size of the residual thyroid tissues to be ablated, the degree of hypothyroidism during the therapy as well as the patients' inherent sensitivity to the treatment.

Administration of nitroglycerine before Tc-99m sestamibi imaging improves tracer uptake in resting hypoperfused regions. The aim of this study was to assess the role of NTG in Tc-99m sestamibi myocardial perfusion imaging of patients with coronary artery disease and previous myocardial infarction and whether it still has a role in cases of severely hypoperfused myocardium. All the thirty five who underwent two Tc-99m sestamibi myocardial perfusion imaging with SPECT, one at baseline and the other after NTG administration (0.6 mg sublingual) at least 24 hours apart were included in this study. All have previous history of

076-PHIIncremental Value of Nitrate Enhancement in Tc-99m Sestamibi Myocardial Perfusion Imaging With Spect In Patients with Coronary Artery Disease and Previous Myocardial InfarctionDuldulao MA, Obaldo JNuclear Medicine Section, Philippine Heart Center, Quezon City, Philippines

Dose Failure Successful ablation P-Value

Low dose (50mCi) 48.6% (17/35) 51.4% (18/35) 1.000 Not Significant

High dose (100mCi) 36% (15/41) 63.4% (26/41) 0.027 Significant

S-46



myocardial infarction and angiographically proven CAD or CAD suspect. Seven out of the total thirty five patients have rest/stress imaging. Qualitative segmental analysis and perfusion scores of each segment were assigned. There was significant reduction of perfusion scores in nitrate-augmented Tc-99m sestamibi compared to baseline (from 30.1 ± 12 to 26.6 ± 11, p<0.0001). The degree of severity at rest was also related to the effect of nitrate, i.e. nitrate administration is more beneficial when mild to moderate defects were seen at baseline study (p<0.002). The overall detection rate of reversible segments with NTG was 44%, observed to be higher in patients without stress-induced ischemia. The degree of stress defects was not related to the effect of nitrates, therefore, even in the presence of severe to absent tracer uptake on stress images, nitrate-enhanced imaging may still be beneficial. Nitrate augmentation has incremental diagnostic value in Tc-99m sestamibi myocardial perfusion imaging in patients with coronary artery disease and myocardial infarction. It potentially improves detection of severely hypoperfused but viable myocardium. The routine use of nitrate in myocardial perfusion imaging should be encouraged especially when selecting patients for revascularization.


The first clinical studies concerning treatment of hyperthyroid patients with 131-I date back as far as 1941. However, it was the following years that brought a wide application of these methods. In Podlasie region (north-eastern Poland) radioiodine treatment was first introduced in 1997. Hyperthyroidism in this region affects about 1.5% of population. The number of new patients is about 3,500 per year. Because iodine deficiency is high in this region, toxic nodular goitre rather than Graves' disease tends to be the main cause of hyperthyroidism. The aim of this study was a retrospective analysis of the results of radioiodine treatment of hyperthyroid patients from 1997 to 2003.From 1997 to 2003, 4913 hyperthyroid patients underwent treatment with 131-I (131-I Polatom, Œwierk) in the Nuclear Medicine Department of the Medical University of Bia³ystok. The tested group included: 2106 patients with single solitary nodule, 1968 with multinodular goitre and 839 with Graves' disease. The diagnosis was made on the basis of physical examination and biochemical test results including TSH, fT4 and fT3. All patients had scintigraphic studies with 24 and 48 h uptake of 131-I. They also underwent ultrasound scans to enable assessment of the goitre size and to discover the nodules. All patients with nodules revealed by physical examination and ultrasound scans had biopsy performed under ultrasonographic control. The therapeutic doses

077-PHIRadionuclide treatment of Liver Cancer using Re-188 Lipiodol: Experience in PhilippinesSan Luis TOL, Ogbac R, Barrenechea E, Ang SSt. Lukes Medical Center, 279 E. Rodriguez Blvd., Quezon City 1102, Philippines

078-POLA Retrospective Assessment of the Effectiveness of Radioiodine Treatment of Hyperthyroid Patients from 1997 to 2003 in the North-Eastern Region of Poland.Budlewski T, Rogowski F, Szumowski P, Parfieñczyk A, Sopotyk A, Kociura-Sawicka A, Abdelrazek SThe Department of Nuclear Medicine, Medical University Hospital, Bia³ystok, Poland

of 131-I were calculated on the basis of iodine uptake, goitre size and an assumed absorbed dose. Marinnneli's formula was applied. The assumed absorbed doses were diversified according to the cause of hyperthyroidism and the size of goitre, and ranged from 80 to 350 Gy. In case of small goitres the absorbed doses varied from 80 to 100 Gy. In case of Graves' disease - from 80 to 150 Gy, in solitary nodules from 200 to 350 Gy. 131-I was given to patients orally in capsules. The administered therapeutic doses ranged from 200 mCi to 800 mCi. Steroid protection was given to patients with Graves' disease and mild opthalmopathy. This consisted of administering Prednisone orally from the third day after radioiodine in doses of 0.5mg per kg for four weeks and then a gradually reduced dosage for the next two months. Follow up examination was performed after 4-6 weeks, then after 2 months, 4 months, 6 months and 12 months after radioiodine administration. These studies involved a physical examination and biochemical tests like TSH, fT3 and fT4. The study group consisted of 4913 patients, including 4244 women (84%) and 769 men (16%) were treated in the Nuclear Medicine Department of the Medical University Hospital of Bia³ystok. Hyperthyroidism caused by Graves' disease was discovered in 17% of the patients, including 597 women and 260 men. Multifocal autonomy - in 40% of patients: 1712 women and 256 men, whereas unifocal autonomy in 43%: 1853 women and 253 men.After 12 months of follow-up, radioiodine therapy proved to be successful in 74% of patients. Hypothyroidism was found in 12 %, and in 14% subclinical and/or symptomatical hyperthyroidism. The best effects were achieved in the group with unifocal autonomy - euthyroid in 92%, a lower effectiveness in multifocal autonomy euthyroid in 87%, and the least successful therapy -72% - in the group with Graves' disease. Due to persistent hyperthyroidism, further radioiodine doses were applied in 28 % of Graves' disease patients, 13% of multifocal autonomy patients and 8 % of unifocal autonomy patients. In case of patients with Graves' disease who were given steroid protection, no increase of opthalmopathy was discovered.Compared to other studies, the presented results of RIT seem to be highly effective. The high therapeutic effectiveness of this method is the result of a suitable preparation of patients and proper doses calculated with consideration for such factors as the radioiodine uptake, the effective half live of 131-I and the size of the goiter. It also results from a specific form of hyperthyroidism in the region: over 80% of hyperthyroidism is caused by unifocal autonomous and multinodular hyperthyroid goiter. The long-term results of RIT in this region will be known once an additional analysis is conducted after a 5 and/or 10 year period.


079-POLIntravascular radionuclide therapy using Re-188 Perrhenate to prevent re-stenosis following PTCA: Initial Experience in PolandBirkenfeld B et alDepartment of Nuclear Medicine, Pomerian Medical University, U1. Unii Lubelskiej 1PL-71-252 Szczecin, Poland

S-47



0


From the number of beta-emitting radionuclides useful in internal radiotherapy several can be produced at the Radioisotope Centre POLATOM either in a carrier-added (153Sm, 166Ho, 186Re) or in a carrier-free form (90Y, 177Lu), based on the locally developed technologies. Recently our efforts were focused on the development of 188W/188Re generator which would provide pharmaceutical grade 188Re. In this paper we present our experience with the preparation of a portable 188W/188Re generator and its stability over the period of several months. The eluate of 188Re perrhenate obtained from this generator has been successfully utilized to produce 188Re-HDEP, a therapeutic agent useful in palliative treatment of painful bone metastasis. The rhenium-188 (T1/2 = 16,9 h) is a beta-gamma emitting radionuclide (Eâmax=2.12 MeV) suitable for therapeutic application while its gamma emission (155keV) allows evaluation of biodistribution of radiopharmaceuticals and radiation dosimetry studies. Radionuclide 188Re is produced in decay of 188W, which in turn is obtained by neutron activation of 186W in a high flux nuclear reactor according to the following

reaction:186W (n, ) 187W (n, ) 188W.For preparation of the generator high specific activity 188W (RIAR, Russia) as well as the alumina column and the shielding (Radioisotope Centre POLATOM, Poland) used for manufacturing of 99Mo/99mTc generators were used. The generator column containing alumina was activated using 0,9% NaCl solution (pH = 3.0). Then the 5,5 GBq of 188W (195 GBq/g W) in the form of tungstenic acid was slowly loaded on the column (flow 0,1 ml/min). After 188W deposition the alumina column was washed with 0,9% NaCl solution (pH = 5.0 6.0). The generator was eluted 2-3 times per week over the period of 6 months. The generator yield was calculated as 188Re activity obtained versus theoretical one. The radionuclidic purity of the

eluates related to the 188Re activity was checked by -spectroscopy. The radiochemical purity of eluted 188Re-perrhenate solution was determined by TLC method and its chemical purity assessed by ICP-Optical Emission spectrometer (Optima 3300 XL, Perkin-Elmer). The elution yield of 188Re calculated on the elution time was well above 80% of the theoretical activity and more then 90% of eluted activity was collected in first 4 ml of the eluate to give radioactive concentrations up to 100mCi/ml . We also observed low level of radionuclidic impurities in eluate (less then 5*10-2 %). The content of 188W (188W break-through) was lower then 2*10-2 %. Only in the first elution the Al concentration was about 200

80-POLSentinel Lymph node mapping and detection in patients of melanoma: Role in prognosisBirkenfeld B et al.Department of Nuclear Medicine, Pomerian Medical University, U1. Unii Lubelskiej 1PL-71-252 Szczecin, Poland

081-POL188W/188Re generator as a convenient source of 188Re perrhenate solution and a kit for preparation of 188Re-HDEHP

1 1 1 1 2Mikolajczak R , Korsak A , Zuchlinska M , Pawlak D , Konior M , 2Zelek Z

21Radioisotope Centre POLATOM, POLATOM Sp. z o.o., Swierk-Otwock, Poland

g ® g ®

g

ppm, but later on did not exceed 10 ppm. To check the suitability of the 188Re eluate for medical purposes, a lyophilized kit preparation of hydroxyethylidenediphosphonate (HEDP) for labelling with 188Re has been developed. To prepare 188Re-HEDP up to 97 mCi in 2ml eluate of sodium perrhenate was added to a vial containing 5.0 mg HEDP, 4.9 mg SnCl2, 2.9

mg ascorbic acid and 0.5 mg KReO4. Then 200 l of 3 M HCl was added to lower pH to 0.5 1. The whole mixture was heated for 15 min at 95?C to 100?C, allowed to cool, whereafter 2.0 ml sodium

acetate solution (39mg/ml) containing 50 l 30% NaOH was added to adjust the pH to 5-6. The radiochemical purity was determined by ITLC-SG using 0.9% NaCl as solvent and paper chromatography using Whatman 1 and acetone as developing solution. Using saline as eluent, 188Re-HEDP and perrhenate move with the solvent front and only reduced colloids or ReO2 remain at the origin, while using acetone, 188Re-HEDP stays at the origin and free perrhenate moves with the solvent front. Stability of 188Re-HEDP was observed when stored at 20-25?C for 1, 2, 3, 24, and 48h. Radiochemical analysis indicated high yields of labelling above 99% when stored at 20-25?C for 24 h, and the labelled compound being stable for 48 h (RCP>96%). We also analysed 188Re-HEDP biodistribution and bone uptake following intravenous injection in Wistar rats to assess its potential for clinical use. It showed that the radioactivity in the bone tissue was as high as 2.68% ID/g at 1 h increasing to 3.32% ID/g at 3h. The activity level in the kidney was the highest at 1 h (0.79% ID/g) but then decreased through the study. Radioactivity in the blood, lung, liver, spleen, and muscle was low (0.23% ID/g the highest of each of these organs) at 1 h and cleared out rapidly. The bone/muscle ratio was 26.8 at 1 h and increased to 55.7 at 24 h.The results of this study showed that using standard alumina column it is possible to produce stable 188W/188Re generator providing 188Re eluate suitable for medical purposes. The preparation 188Re-HEDP is sufficiently stable, high level of deposition in bone was observed while injected intravenously to healthy rats. The kit formula for preparation 188Re-HEDP provided an alternative promising radiopharmaceutical to treat and diagnose bone metastases.

The clinical use of radiations was envisaged soon after the discovery of X-ray by Wilhelm C. Röntgen in 1895. During decades, radiations were used on an empirical basis lacking rigor in dosimetry and radiation protection. These difficulties have been surpassed as the scientific knowledge and technology progressively developed. Energy from radiation may be delivered externally or internally. In the later case, solid implants into or next to the targeted tissues are used for a short period of time or on a long term (brachytherapy). Radiotherapy planning is of primordial importance, because it is necessary to ensure that a therapeutic radiation dose is delivered to a defined three-dimensional target volume, while effects on the surrounding healthy tissues are to be minimized. Several models for the quantification of biologic radiation response concerning dose, dose-rate, and number of dose fractions, total irradiation time etc. were developed. The most commonly used is the linear quadratic (LQ). It is based on sub-cellular biophysical events and combined with clinical experience in order to provide a guideline for external

m

m

082-PORTherapeutic RadiopharmaceuticalsM. Neves. A. Kling and A. OliveiraInstituto Tecnológico e Nuclear, Estrada Nacional no.10, 2686-953 Sacavém, Portugal

S-48



radiation therapy and brachytherapy in the form of a therapeutic index.Internal radiotherapy with radiopharmaceuticals Targeted Radiotherapy (TR) - has so far played a relatively small role in nuclear medicine practice. It was restricted to the use of iodine-131, developed more than 50 years ago for the treatment of thyroid cancer. In the past few years, TR has seen a rapid growth as a consequence of improvements in tissue specific biomolecules, and its potential advantages over external and solid implants. In particular, for patients with inoperable or multi-site disease it is an effective complement or alternative to chemotherapy. Since TR requires the administration of significantly higher activities than in diagnostic applications a larger number of exigencies are necessary: high target binding, uniform target distribution, minimum irradiation of critical organs, effective biologic dose response, precise estimation of radiation dosimetry, radiation protection safety, etc. Therefore, substantial efforts in several research areas as: radionuclide production, radiopharmaceutical chemistry, medical physics and radiation biology, etc are required. TR is based on the selective deposition of cytotoxic ionizing radiation from the radionuclides attached to the specific biomolecules that damages or destroys cells. Since differences in radiosensitivity among tumour cell types can decide on the success or failure of targeted radiotherapy, the following additional aspects have to be considered: i) The appropriate radiation absorbed dose (which should match the biologic desirable effect), and consequently the properties of the radionuclide emissions (type of radiation, energy and half-life); ii) The biological response, i.e. the response of cells to radiation as radiosensitivity, repair capacity and proliferation rate or repopulation; iii) The continuous refinement of nano and microdosimetry in order to increase the accuracy and the dose/response correlations.In conventional radiotherapy, the terms low, medium and high dose rates are still common, but in TR these terms have no more specific meaning since it is possible to exploit subtle differences in the radiation doses provided by a wide range of radionuclides. The role of a radionuclide is to deliver a cytotoxic absorbed dose, sufficient to overcome the cells response in terms of repair and proliferation. In addition, only a minimum absorbed dose should be delivered to the surrounding healthy tissue. The absorbed dose delivered to the cancer cells by a radionuclide should be intrinsically related to the radiobiology response in terms of the relative ability of different tissues to recover from radiation damage and the absolute ability to control concurrent tumour re-growth. As each human cancer has its own cellular cytoxicity and cytoprotective response to ionizing radiation a certain energy threshold has to be surpassed to achieve the cell death. This means that a tailored radionuclide should exist that is able to provide the desired therapeutic effect. The energy threshold depends on several chemical/ biochemical factors (carrier molecule, target affinity, cell distribution, biokinetics, route of administration, radiation safety, etc.) although the radionuclide properties play one of the most important roles. Different half-lives imply different dose rates, resulting in very different clinical response for a given total dose if the surviving cells in the irradiated volume are continuously proliferating, and the sub-lethal damaged cells can be repaired during the protracted dose delivery. Therefore the principles of radiobiology, dose rate and absorbed radiation doses are the most important in order to predict the radiation effects. Radionuclide selection for TR should not be solely based on their availability, but on an analysis of what would be best in terms of radiobiology.

A large number of potential therapeutic radionuclides that emit low energy (conversion and Auger), intermediate and high energy

-electrons ( emitters), and -particles are known. In general, TR of small targets like single cells or small clusters of cells, require short-range high-LET radiation as -particles or Auger electrons emitters with energies below 40 keV. As the radiobiological response depends on the location at which the decay is taking place and as radiopharmaceuticals are never deposited to 100% on

-the targeted organ or tissue, the choice between of - and -emitters should be done criteriously. The use of positron emitting

radionuclides such as Cu-64, In-114m, I-123, Tb-149, Hg-195m etc. for TR is questionable since the interaction of positrons in tissues results in the 511 keV annihilation photons. These constitute a major contribution to the absorbed dose in the surrounding healthy tissues. Nevertheless, positron emitters may be valuable for the selection of radioimmunotherapy candidates by confirming tumour targeting and/or estimating radiation doses.Since the biodistribution and pharmacokinetic differ according to the labelled molecule, dosimetry is much more complex. TR is a form of continuous radiation delivery, during which the dose rate is not constant but rises quickly from zero to a maximum value and then slowly decreases to zero. The linear-quadratic radiobiological model may be applied for TR optimisation to select a near-optimal radionuclide in terms of an appropriate biological response. The radiobiological processes and the LQ formalism are essentially the same for all radiotherapy forms, but in the case of TR dose-limiting values are imposed by the irradiation of critical organs.A list of 64 radionuclides, including 20 new potential candidates for TR is presented in terms of the suitability of their energies for killing tumour cells which grow as single, small, intermediate and large clusters. The new 20 potential radionuclides can also be considered appropriate for intracavitary, intratumoral or permanent implants.

Serum thyroglobulin (Tg) is an important marker in the follow up of differentiated thyroid cancer (DTC) patients. Raised Tg level in the presence of negative antithyroglobulin antibodies is an indicator of persistent or recurrent DTC.The aim of the study was to evaluate the results of the radioiodine treatment in patients suffering from DTC and negative radioiodine scintigraphy (RIS) but elevated serum Tg levels.The study group included 78 patients treated in our hospital between 2000 and 2004, age range 18-74 years, 57 papillary and 21 follicular thyroid cancer. All of them underwent a total or near total thyroidectomy and received 50-100 mCi I-131 therapy for ablation and a second dose approximately 25% higher than the first one. After a negative RIS (5 mCi of iodine-131) for metastases or thyroid bed remnants and serum Tg>3ng/ml (after thyroxine withdrawal and thyroid-stimulating hormone level more than 30ìIU/ml) the patients received an empiric dose of 100mCi of iodine-131; 14 patients were administered >100 mCi because lymph node metastases or pulmonary metastases were seen on ultrasonography , Rx, CT. Patients were followed-up by physical examination, Tg and RIS every 6 months or yearly for

083-ROMRadioiodine therapy of differentiated thyroid cancer in patients with negative diagnostic I 131 scintigraphy and high serum thyroglobulin levelGherghe M, Goldstein A, Dumitriu L. Sf. Ioan Clinical Hospital, Bucharest, Romania and National Institute of Endocrinology “C.I. Parhon”, Bucharest, Romania

S-49




(48%) patients (lymph node metastases in 27 patients, pulmonary metastases in 11 patients).The RITS of the patients who received two or more doses showed improvement in 16 patients ( normal scan or lesser activity than in the previous RITS), there were no changes in 14 patients and in 6 patients the disease progressed.The pre-treatment serum Tg level was 3-1584 ng/ml; no important variations of the Tg level were observed during follow up; however, in 12 patients Tg decreased, in 57 remained at the same level and in 9 patients serum Tg increased. Four patients died during follow up.As a conclusion in patients with negative RIS and elevated serum Tg levels, empiric treatment with radioiodine is recommended because post-therapeutic scans were positive in 48% of the patients. The benefit of the empiric treatments with iodine-131 was demonstrated in the RITS of 16/36 patients that received two doses at least. So, we think empiric radioiodine doses may be successful administered in patients with previously RITS positive. The negative RIS is possible to be caused by low dose of I-131 that is a poor imaging agent for the modern gamma camera so the detection of small or weakly iodine avid metastases is likely to be better at therapeutic doses. But the diagnostic dose cannot be increased because of stunning. The alternative is to use I-123 for diagnostic with better imaging properties, but unfortunately this is not available in our country.

Bone metastases are the most common cause of pain in patients with cancer, and postmortem studies have been shown that up to 85% of patients with breast or prostate cancer have bone metastases at the time of death. The palliation of bone pain is one of the goals of treatments in oncologic patients, due to the fact that patients with bone metastases may survive many years with severe pain and serious impaired mobility. Bone pain palliation can be attempt by using different modalities analgesics (nonsteroid, opioides), biphosphonates, external beam radiotherapy or radionuclide therapy. The aim of our study was to review the database and to analyze the results of the treatments performed in our department, in the field of radionuclide metastatic bone pain palliation with 89Sr 12 patients (47-73 years old) were treated with 89Sr in the past two years in our department. All patients had confirmed prostate adenocarcinoma and refractory bone pain due to skeletal metastasis involving more than one site, associated with osteoblastic response on bone scan. All patients had a good hematological and renal status (Hb> 9 mg/dl, leukocytes > 4000/ ìl, platelets > 150.000/ ìl, GFR > 30 ml/min), an increased alkaline phosphatase and recent bisphosphonate therapy interrupted within 48h before treatment. The standard administered dose was 150 MBq [4 mCi] of 89Sr (Metastron Amersham). In 8 cases single dose was given, while in 4 patients a second dose was administered at 4, 6 and 9 months after the first injection. Clinical and biological evaluation was repeated at 3 weeks and 3-6 months after treatment. Hematological assessment was performed monthly at all patients.The most important criterion of pain relief was objective pain

084-ROMUse Of Sr-89 For Bone Pain Palliation: Experience In Our DepartmentMititelu MR, Mazilu C, Rimbu A, Ghita ST, Marinescu G, Codorean ICentral Clinical Emergency Military Hospital, Dept. of Nuclear Medicine, Calea Plevnei 134, sector 6Bucharest, Romania

score. Significant improvement of life quality was seen in 4 patients with major reduction of analgesic needs. In 4 patients in addition to external beam radiotherapy we obtained a stable effect of more than 6 months. 3 patients had moderate response, one of them with an early need of a second dose at four months. No response was seen in one patient. Pain flare occurred in 7 cases (58.3%). The most serious side effect noticed at these patients was myelosuppression, which occurred in 9 patients (75%), 2 of them receiving transfusion.Respecting the criteria of evaluating patients who might be candidates for treatment using 89Sr, the significant clinical improvement of life quality can be obtained with an easy procedure, controllable side effects and a good compliance of patient. In a country with limited resources for an extensive medical research it is important to introduce new strategies of treatment that have proved their efficacy, to try to promote the cost effective use of high quality therapeutic procedures and the recommended guidelines.


In the preevaluation and diagnosis of the patients with liver tumors, significant nuclear medicine methods used are: radiocolloid, blood pool, hepatobiliary scintigraphy, angioscintigraphy with radiolabeled microspheres as well as «first pass» radionuclide angiography, which can preceede all of the above mentioned methods, during single injection application. The aim of the study is evaluation of the possible role of the scintigraphic estimation of the relative liver perfusion in the choice of treatment of liver carcinomas.The study was performed in 120 patients: 24 controls (C), 35 with benign liver tumors (BT), 35 with hepatocellular carcinomas (HCC), 19 with metastases of colorectal carcinomas (MCC) as well as 7 with metastases of other tumors (MOT-bronhus, lung carcinoma and lymphoma). 7/35 HCC had cavernous portal vein developed after tumor thrombosis, 2 had complete thrombosis and 5 had incomplete thrombosis (thrombosis of the either of portal venous branches (3) and incomplete portal venous thrombosis -2). 2/19 patients with MCC had cavernous portal vein developed after tumor thrombosis, 3 had complete portal venous occlusion and 4 incomplete thrombosis (thrombosis of the either of branches).The study was performed with ROTA scintillation camera and Micro Delta computer, during 60 sec (1f/sec) from i.v.application of 740 MBq 99mTc-pertecnetate. TA curves were generated using

085-RSATreatment of Hyperthyroidism with Radioiodine: comparison of the efficacy of low, medium and high doses of I-131, with special emphasis on the socio-economic issues related to the treatmentA. Ellmann et alDept.of nuclear medicine, Tygerberg Hospital, 7505- Tigerberg, South africa

086-SERPossible Role of the Scintigraphic Estimation of the Relative Liver Perfusion in the Choice of Treatment of Liver CarcinomasArtiko V, Obradovic V, Davidovic B, Petrovic N, Vlajkoviæ M, Kostic KInstitute for Nuclear Medicine, Clinical Center of Serbia and Department of Nuclear Medicine, Clinical Center Niš, Serbia and Montenegro

S-50



liver ROI, spleen ROI and left kidney ROI, and curves were generated. Hepatic perfusion index was calculated using slope analysis (Portal slope Ps and arterial slope As) method according to following formula HPI=Ps/(Ps+As). Complementary methods used were Doppler ultrasonography, CT, MRI, tumor marker assays (CEA, Ca19-9, AFP) laboratory analyses, pathohistological finding and clinical diagnosis.In C, HPI was 0.68±0.06 which did not differ from the value in BT (0.64 ±0.08) (p>0.05). However, in HCC ( X=0.26±0.20), and LM (X=0.40±0.28), HPI values were significantly decreased in comparison to C and BT (p<0.01), but they didn't differ between themselves (H-LM, p>0.05). In 7/35 HCC with cavernous portal vein developed after tumor thrombosis values were nonsignificantly lower (X=0.21±0.12, p >0.05) than in HCC, in 2 with complete thrombosis values were significanly lower (HPI=0, p <0.01) and 5 with thrombosis of the either of portal venous branches and/or incomplete portal venous thrombosis values were significanly lower than those in HCC (HPI=0.17±0.09, p<0.05). In 2/19 patients with MCC and cavernous portal vein developed after tumor thrombosis, HPI was nonsignificantly lower than in MCC (HPI=0.32±0.17, p>0.05), in 3 with complete portal venous occlusion values were significantly lower than in MCC (HPI=0, p<0.01) while in 4 thrombosis of the either of branches they were significantly lower than those in MCC (HPI=0.25±013, p<0.05).HRA could be easily done during the different conventional nuclear medicine methods used in diagnostic process and in the pre-treatment evaluation. In addition, it can be an useful method for the assessment of different degrees of hemodynamic alterations in portal system, for differential diagnosis of benign and malignant liver tumors, as well as for assessment of the liver tissue and tumor perfusion, which might be helpful in the decision

131 90making for the undertaking of intraarterial I -lipiodol or Y-colloid therapy. It is particularly suggestible because of the fact that this therapy is mainly recommended in the unresectable and untransplantable patients with portal venous occlusion and mainly arterial vascular supply. Thus, by this noninvasive method, it could be able to avoid invasive and complicated (especially in the patients with impaired coagulation factors) recommended study of portal backflow by injection of an iodinated hydrosoluble radiological contrast agent into the splenic or superior mesenteric artery, which is a

131preliminary study for the selection of the patients for I ethiodized oil therapy. It could also be used for evaluation of the

131efficacy and safety of hepatic intraarterial injection of I iodized oil in the treatment of liver carcinomas in patients with impaired portal venous flow, for the evaluation of its effect on the tumor itself, as well as its effect on the tumor thrombi in the portal vein which are also arterially vascularized. This method will also allow the selection of the patients on the basis of tumor vascularisation, and reject from the procedure those (minority) with predominantly portal vascularisation, or mainly arterial but with insufficient supply. Also, this procedure will allow the exact estimation of the portal venous occlusion, suggestible for the procedure.

087-SERIs drug-free period prior to radioiodine therapy decisive for treatment outcome in patients with multinodular toxic goitre?

Han R, Beatovic S, MarkovicS, Jaksic EInstitute of nuclear medicine, Clinical Centre of Serbia, Belgrade, Serbia and Montenegro

It is known that radioiodine treatment of benign thyroid diseases is accepted as a first line therapy in many nuclear medicine institutions but the methods, doses and eventual premedications are still a matter of debate. In a number of institutions patients with thyrotoxicosis are treated with anti-thyroid drugs before radioiodine therapy in order to deplete the thyroid gland of preformed stores of hormones. Such approach may prevent potential cardiovascular events particularly in elderly. This is mostly true for patients with multinodular toxic goitre (MNTG).

131Concerning the final I therapy outcome in these patients, existing literature data are not sufficient and by some means controversial. It is known that anti-thyroid drugs diminish serum levels of antithyroid antibodies and iodine uptake. In addition, some of them particularly those with sulfhydril group such as propylthiouracil (PTU) may increase glandular radio resistance. The purpose of this analysis was to examine whether drug-free period in patients with MNTG and treated with PTU is of any influence on the final outcome of radioiodine therapy. In retrospective study, medical records of 300 patients (m=74, f=226, mean age: 55 +/-12 years) suffering from MNTG and

131treated with I where analysed. Patients were divided in two groups. In group A were 120 patients (m=29, f=91) in which

131therapy with PTU was withdrawn 4 to 6 weeks prior to I therapy. In group B were 180 patients (m=45, f=135) treated with the same

131drug incessantly up to the day of I therapy. Except for PTU all patients were using propranolol as adjuvant therapy. Two weeks prior to radioiodine therapy patients were instructed not to take

131iodine containing drugs and iodine-rich food. Water solution of I (sodium iodide) was administered orally in an average doses of 380 MBq (range 296-470). Clinical status and thyroid hormones

131levels were assessed 3,6 and 12 months after the I therapy. At one year after the therapy patients were classified into three groups according to clinical status and serum levels of thyroid hormones as hyperthyroidism (failure of the therapy), euthyroidism and hypothyroidism. Thyrotropin (TSH), FT4 and FT3 were measured by DELFIA. All assays were calibrated against acknowledged international reference standards. Thyroid iodine uptake was

131measured 3h and 24h after per oral intake of 0.5 MBq I. Thyroid volumes were estimated by palpation and ultrasound by one experienced thyroidologist. The differences between two groups were assessed by the Student's t-test. Non-parametric rank tests were used to evaluate differences in final outcomes amongst two groups of patients. A p value of less than 0.05 was considered as statistically significant. No significant differences were found between two groups of patients in terms of age, gender, volume of the thyroid and mean

131PTU doses (100 ± 25mg) prescribed. Before the therapy I uptake and levels of thyroid hormones were significantly lower in group B, so all patients in this group were biochemically euthyroid. Clinical status of patients from group A, one year after radioiodine therapy was as follows: failure of the therapy was found in 11 (9%) patients (m=3, f=8), euthyroidism in 99 (83%) patients (m=22, f=77) and hypothyroidism in 10 (8%) patients (m=4, f=6). Clinical status of patients from group B, one year after radioiodine therapy was: failure was found in 32 (18%) patients (m=10, f=22), euthyroidism in 142 (79%) patients (m=32, f=110) and hypothyroidism in 6 (3%) patients (m=3, f=3). Failure rate was significantly higher in group B as well as a lesser degree of hypothyroidism. Significantly higher rate of hypothyroidism was found in group A. Patients were a bit more likely to be euthyroid after 12 months if they were clinically and biochemically euthyroid on the day of radioiodine therapy. No patients developed thyroid related orbitopathy. Relatively low rate of

S-51


hypothyroidism in both groups of patients is most likely due to iodine uptake restricted only to hyper functioning tissues in the multinodular thyroid gland. Following the results of this single and relatively uniform therapeutic protocol, it may be concluded that euthyroid clinical status was found in nearly the same proportion in both groups of patients, regardless of the premedication prior to radioiodine therapy. Higher failure rate in patients treated with PTU up to the day of radioiodine therapy could be explained by higher radio resistance of thyroid tissue but, in these patients hypothyroidism is less likely to develop. Although the exact role of premediaction with PTU in clinical practice is still unclear and needs further study, we suggest that such approach is advisable in patients with MNTG particularly in older and with known or susspected cardiovascular disease.

Polycythaemia Vera (PV) is a clonal progressive myeloproliferative disease, which is characterised by an autonomous proliferation of marrow cells and can be treated by phlebotomy and cytoreductive therapy. The aim of this study was to review the radionuclide therapy using P-32 orthophosphorus in the treatment of the patients with PV and Essential Thrombocythaemia (ET). During past ten years 21 doses of P-32 were administered in 15 patients mean age 61.4 years (43-77) with PV and ET. In all of them the diagnosis of myeloproliferative disease PV or ET was confirmed by haematologists using standard criteria. Red blood cells volume meassuring using 99m Tc labelled erythrocytes was performed to facilitate the diagnosis. Patients were considered for P-32 administrations after than they have failed treatment by phlebotomy and chemotherapy. After phlebotomy of 300ml fool blood if necessary, patients were injected by P-32 fixed dose activity of 3 mCi per m2, increased up to 5 mCi for the additional one, intravenously via canula to avoid extravasations. Full blood count in monthly interval was used for monitoring the patients and asses the response to therapy. The average duration of disease between the time of establishing the diagnosis and P-32 administration was 22 months. Among 15 patients injected by P-32 orthophosphorus, in six of them two doses of P-32 were administered in the median interval of 24.7 months. Complete remission was observed in 11 patients and partial remission in four patients at the end of the first year of therapy. There was no report of the development of acute myelogenous leukemia in treated patients. Thrombotic events were registered in 2 patients. It is concluded that administration of P-32 was shown as effective, inexpensive and simple modality of disease control in patients with Polycythaemia Vera and Essential Thrombocythaemia. Closer cooperation between hematologists and nuclear medicine specialists would be necessary in the follow up of patients for adequate documentation of side effects and complications due to P-32 treatment.

088-SERP-32 Orthophosphorus in the Treatment of Polycythaemia Vera and Essential ThrombocythaemiaJaukovic L, Ajdinovic B, Jankovic Z, Pucar DInstutute of Nuclear Medicine, Military Medical Academy, Crnotravska 17, BelgradeSerbia and Montenegro

089-SIN[Re(CO)3]-Chelates as Therappeutic Radiopharmaceuticals for the treatment of Hepatocellular CarcinomaSaw MM et alDepartment of Nuclear Medicine, Singapore General Hospital, Singapore

090-SINExperimental therapy with P-32 for hepatomaGoh A et alDepartment of Nuclear Medicine, Singapore General Hospital, Singapore

091-SINRadioimmunotherapy of Refractory B-Cell LymphomaSundram FX et al.Department of Nuclear Medicine, Singapore General Hospital, Singapore

092-SLKEvaluation of the Efficacy of Radiosynovectomy in Rheumatoid Arthritis and Haemophilic Arthropathy (CERAHA): First Results of an IAEA Co-ordinated Research Project (CRP) Vereb M, Kaliska L. Department of Nuclear Medicine, Hospital Poprad, Banícka 803/28, Poprad, Slovakia and Department of Nuclear Medicine, Roosevelt Hospital, L. Svobodu 1, 975 17 Banska BystricaSlovakia




The main objective of the study was to determine the therapeutic efficacy of radiosynovectomy. Rheumatoid arthritis is a Chronic or sub-acute, systemic inflammatory disorder principally involving the joints with peripheral symmetrical inflammatory non-suppurative arthritis. It usually has a prolonged course with relapse and remissions. Haemophilia is a congenital blood disease that produces abnormal bleeding at musculoskeletal level. The origin of this abnormal bleeding is the lack of a coagulation factor, Factor VIII for haemophilia A and Factor IX for haemophilia B or Christmas disease. The overall goals of therapy in rheumatoid arthritis are: alleviation of pain, control of disease activity, slowing down the rate of damage and improvement in the quality of life. On the other hand the aim of the orthopaedic treatment in haemophilic haemarthrosis is to avoid recurrence of the haemarthrosis by acting on the synovial membrane, by fibrosing it, in addition to pain alleviation and improving the quality of life. Radionuclide therapy, commonly known as “Radiosy- novectomy”, is a very useful procedure, which if used appropriately may form an effective tool in the management of rheumatoid arthritis and haemophilic haemoarthropathy. With the help received from the IAEA under the auspices of a coordinated research project, for the first time in our hospital we introduced radiosynovectomy in the year 2003. Until now, a total number of 40 patients of rheumatoid arthritis and one patient of haemophilic arthritis have been treated following a protocol designed by the IAEA under the CRP. The diagnosis of rheumatoid arthritis and haemophilic arthropathy was established by standard well

S-52



established findings of clinical examination and laboratory investigations. All patients underwent a two phase bone soft tissue scintigraphy to assess the inflammatory activity in the joints prior to therapy. A radiosynovectomy team was formed in the hospital consisting of a nuclear medicine physician, orthopaedic surgeon and a rheumatologist. In our hospital in most instances the intraarticular procedures were performed by our consultant orthopaedic surgeon. The results are now being analysed. Although we have seen good results in most of our patients along with significant improvement in quality of life, the rheumatologists and orthopaedic surgeons of our hospital are still inclined to perform surgical procedures over radiosynovectomy. The procedure of Radiosynovectomy is simple requiring only minor intervention. It is less expensive than any other therapy. It can be performed on an out-patient basis and can be effective in those patients who are refractory to medical therapy, as well as in those who are not suitable for surgical therapy. The procedure does not require any rehabilitation process; it is possible to treat multiple joints simultaneously or at short intervals. It is therefore recommended as an important mode of treatment in patients of painful arthropathy. It is hoped that with time this procedure will gain more and more acceptance in our region and get integrated into the routine health care system to benefit more and more needy and deserving patients suffering from painful joints.

In Slovenia 1260 radionuclide therapies are performed per year for a population of 2 000 000 (63/100 000 inhabitants). Approximatelly half of the patients (691) were treated as outpatients. There are 7 nuclear medicine departments in the country and 4 of them are licensed to perform radionuclide therapy and two have specialised wards for patients receiving radionuclide treatment (10 beds).131-I is used by far most commonly for benign thyroid diseases and differentiated thyroid Ca treatment. The patients receiving doses of radioactivity below 550 MBqs, i.e. mostly patients with Graves´ disease, are treated as outpatients i.e. 610/year, (31/100 000 inhabitants). The patients treated with doses between 740 1110 MBq, mostly hyperthyroid patients with autonomous thyroid tissue (Plummer´disease), 300/year (15/100 000 inhabitants) are hospitalised for 3 5 days in a speciaised wards. (Fractionated therapy is not used). 137 therapies were performed for ablation and treatment of metastases in patients with differentiated thyroid cancer receiving 1850 5550 MBq, in 2004 as inpatients. 131-I mIBG is used for treatment of neuroblastoma very occasionally, less than 1/year due to low number of patients. Such patient has to be hospitalised in an adult radiotherapy ward, a situation not prefered by paediatritians. 186-Re HEDP, 153-Sm EDTPM and 89-Sr were used for paliation of bone pain due to bony metastasis usually as outpatients, depending on patient´s condition, in only 14 patients in 2004. 186-Re colloid and 90-Y colloid are used for radiosynovectomies in patients with rheumatic and (32/year) and hemophilic (25/year) arthropathies. These patients are not hospitalised.5 patients were treated with 90-Y anti CD20 MoAB for NHLymphoma, all on outpatient basis and 2 patients received 90-

093-SLORadionuclide Therapy in SloveniaFettich J.University Medical Centre Ljubljana, Slovenia

Y Octreotide for metastatic carcinoid also as outpatients.12 patients received 90-Y colloid intraperitoneally for experimental treatment of carcinosis due to ovarian Ca in 2004 (scientific study protocol, not used routinely).Radionuclide therapy is genarally well acepted in Slovenia. Nevertheless more widespread use is restricted by poor co-operation and comunications with oncologists (bone pain paliation), logistic problems (intraarticular injections in case of rheumatiod arthritis patients), lack of proper radiotherapy wards (all 131-I therapies above 550 MBq) and high cost (e.g. 90-Y anti CD20 MoAB).

Radiosynovectomy is a potentially effective method for treatment of recurrent hemarthrosis in patients with hemophilia, and can prevent the onset of hemophilic arthropathy.Aim: to ascertain the effectiveness of radiosynovectomy in patients suffering from hemophilic hemarthrosis, to determine the effect of treatment on clotting factor consumption, and to find out how the patients experience radiosynovectomy. 26 radiosynovectomies were done in 21 patients. Four joints were treated twice and one patient had 2 joints treated at the same time. 90 186Y colloid was used for the knee joint (8 joints) and Re colloid for ankle, shoulder and elbow radiosynovectomy (18 joints). The patients were followed for one year after therapy using a questionnaire. During the first year following radiosynoviorthesis as compared to the year prior to the therapy the outcome of treatment was excellent in 11%, and good in 42% of cases. The number of hemarthroses fell from 13 ± 8 to 7 ± 6 per year, and the consumption of the clotting factor declined by 13,200 I.U./year on the average. In joints with 12 or more bleedings the number of hemarthroses fell from 21 to 7 on the average. The outcome of treatment was excellent in 25%, and good in 37% of cases. A mean decrease in clotting factor consumption in the group was 25,800 I.U. In joints with less than 12 bleedings, the number of bleeding episodes declined by 1, and the saving effected in the consumption of clotting factor was negligible. After the treatment, 55% of patients had no adverse reactions; 37% had mild transitory swelling and 7% developed moderate transitory swelling of the treated joint.It was concluded that radiosynovectomy is an effective method for the treatment of hemophilic hemarthrosis, particularly in patients with frequent intra-articular bleedings. In patients with frequent bleedings into joints the consumption of the clotting factor was reduced significantly only. Radiosynovectomy is well accepted by patients suffering from hemophilic hemarthrosis.

0

A serum TSH level of > 30 mU/L, which is necessary for reliable

O94-SLOThe Efficacy of Radiosynoviectomy in Hemophilic Hemarthrosis According to the Frequency of Joint BleedingsGrmek M*, Brecelj J**, Fettich J**Dept for Nuclear Medicine, **Dept. for Orthopedic Surgery; University Medical Center Ljubljana, Slovenia

95-SLORecombinant Human TSH (rhTSH)- Aided Radioiodine Therapy in patients with metastatic differentiated thyroid carcinoma Results 2002-2004

1 1 1 2Schwarzbartl-Pevec A , Vidergar-Kralj B , Zagar I , Besic N1 2 Department of nuclear medicine, Department of surgery, Institute of Oncology, Ljubljana, Slovenia

S-53



testing and efficient radioiodine therapy in patients with differentiated thyroid carcinoma, may be achieved by: a 4-6 weeks L-thyroxine withdrawal or by application of recombinant human TSH (rh TSH).The purpose of our study was to test the efficacy of 131-I therapy (RAIT) using recombinant human TSH (rhTSH) as an alternative in patients with differentiated thyroid carcinoma (DTC) in whom endogenous TSH stimulation was not an option due to the poor patient's physical condition during the hypothyroid state or due to the disease progression during L-thyroxine withdrawal.The study comprised 14 patients (12 females, 2 males, aged 63-81, median 73 years), with histologically proven DTC, in whom the primary diagnosis was established 1993-2000, who already have undergone total or near-total thyroidectomy and who have received radioiodine ablation and 3-12 (median 6) RAITs after L-thyroxine withdrawal, with a cumulative dose ranging 15.65-68.34 GBq.Patients were given 28 RAITs (7/14 patients received two, 2 received 3 and 1 received 4) while on L-thyroxine after rhTSH administration (rhTSH RAIT). RhTSH (0.9 mg, i.m.) was administered on two consecutive days, followed by 131-I therapeutic dose (5.2-7.6 GBq) administration on the third day and a post-therapeutic whole-body scan (PTWBS) 2-5 days later. The efficacy of rhTSH RAIT was evaluated by thyroglobuline (Tg) measurement 3 - 6 months after rhTSH RAIT.Serum TSH levels after rhTSH administration were 61 - 305 mU/l. Altogether 36 131-I-avid lesions were detected on PTWBS. In one patient who underwent two rhTSH RAITs a decrease of 131-I uptake in one lesion was seen on the second PTWBS. In all patients serum Tg concetrations were elevated before rhTSH RAIT (25 -17248 ng/ml). Three months after therapy serum Tg decreased by 24 -91% in 6 cases (4 patients), in 3 patients serum Tg stagnation was achieved, while in 7 cases the disease progressed (serum Tg increased upto 131 - 190% baseline level ). The rhTSH was well-tolerated. Two patients had mild nausea and/or headache, two experienced pain in the bone metastases, another two experienced a “flu-like syndrome”. It is concluded that RhTSH RAIT may be effective in metastatic DTC patients who otherwise could not be efficiently treated with 131-I. However, the diversity of other therapeutic approaches (previous RAITs under endogenous TSH stimulation, external-beam radiotherapy, chemotherapy) even in a well-responding patients did not allow us to attribute the tumor and metabolic response just and only to the RAIT under rhTSH stimulation.

0

Struma ovarii is a rare ovarian germ-tumor, consisting mainly of thyroid tissue, comprising up to 2% of all ovarian tumors. In 2-5% of all cases it is malignant. Approximately 5% of all malignant ovarian strumae metastasize, mainly to the peritoneum and liver. We report a case of a 59-years-old female, who presented with vague abdominal pain. She had a history of an abdominal operation at age of 39 (when 3 months pregnant) for a septated cystic ovarian tumor in the ileocecal region, that contained a dermoid cyst. Neither the definite histopathological finding, nor the TG value at the time of operation were available. Physical

96-SLOAnother case of Metastatic Malignant Struma Ovarii? A case report of good response to Radioiodine Therapy

1 1 1 2Žagar I , Vidergar-Kralj B , Schwarzbartl-Pevec A , Besic N1Department of Nuclear Medicine, Institute of Oncology

2Ljubljana, Slovenia and Department of Surgery, Institute of Oncology Ljubljana, Slovenia

examination at presentation, pelvic US and CT of the abdomen revealed a new tumor in the ileocecal region. Its primary origin in the gastrointestinal tract was ruled-out by gastroscopy and colonoscopy. Explorative laparotomy revealed a right-sided tumor of the omentum, a 2.5 cm large lymph node in the ileocecal part of the omentum and additional smaller lesions, upto 2 cm in diameter, disseminated througout the abdomen these were histologically proven to be metastases of a well-differentiated, follicular thyroid carcinoma. A 14 x 18 mm large nodule in the right thyroid lobe was ultrasonographically, scintigraphically and cytologically non-suspective of malignancy. Taking into account the abdominal metastatic spread, the primary follicular carcinoma in the thyroid gland seemed less probable than the primary arising from struma ovarii. Extensive surgical removal of the abdominal metastases was followed by the near-total thyroidectomy, that revealed no evidence of malignancy in the thyroid tissue thus making the struma ovarii more probable and by ablation with 3.7 MBq 131-I. Post-ablation WBS (at TSH > 30 mU/L, Tg 9.5 ng/mL and anti-TG antibodies 173.78 U/mL) has shown 131-I uptake in thyroid tissue remnants bilaterally and pathologic tracer uptake in the mid- and left hypochondrium, right mesogastrium and median and right pelvis. Thyroglobulin value 3 months after RI ablation, both while on L-thyroxine suppression and under endogenous TSH stimulation, preceding second (therapeutic) 131-I application, were 0.2 ng/mL, however with high anti-TG antibody titres (507.63 and 277.8 respectively). A post-therapeutic WBS, 48 hrs post 5.5 GBq 131-I and 4 months after ablation, has again shown faint uptake in the thyroid tissue remnants, but demonstrated a complete regression of the intra-abdominal lesions. The patient is now, during a 16 months follow-up period after the last radioiodine application, euthyroid. She is clinically and biochemically with no evidence of the disease. The case demonstrates the necessity of combined surgical and radioiodine treatment in malignant struma ovarii and the importance of long-term follow-up after the initial surgery.

Differentiated thyroid cancer (DTC) remains one of the curable of all cancers. All literature reviews and clinical experiences

131regarding I use in DTC conclude the beneficial effects, better prognosis, longer survival time and an assurance for cure. The Overall prognosis of patients with DTC is excellent if treat scientifically, adequately and timely. The management of thyroid cancer depends on the resources available in different institutions. Nuclear Medicine unit (NMU), Faculty of Medicine Peradeniya, Sri Lanka is in the process of uplifting the services for thyroid cancer management. Clinical audit was carried out in NMU on patients who utilized the Nuclear Medicine facilities in the management of DTC. It is important to identify deficiencies in current practice to improve our services.During January 2004 to March 2005, 126 DTC patients were referred for radioiodine Whole body scan (WBS) and therapy. Their age, sex, histology, extent of surgery, adequacy of thyroxine suppression treatment, monitoring with serum thyroglobulin levels (Tg), WBS results and radioiodine therapy were analyzed. There were 104(82.5%) females and 22(17.5%) males giving sex

097-SRLRadioiodine (I-131) application in the management of differentiated thyroid cancer (DTC) AuditNanayakkara DNuclear Medicine Unit, Faculty of Medicine, University of Peradeniya, Sri Lanka

S-54



ratio of 4.7: 1. The Mean age was 35.5 years (range 9-58 years). The commonest histological types were papillary carcinoma 55.5% (n=70), follicular carcinoma 35% (n=44) and follicular variant of papillary carcinoma 9.5% (n=12). Seventy five percent (n=95) had total thyroidectomy (TT), 17 %(n=21) had near total thyroidectomy (NTT) and 8%(n=10) had subtotal thyroidectomy (STT). Sixty-nine patients (54.8%) were on thyroid suppression therapy. Thirty-six patients (28.6%) were referred to the WBS soon after surgery without initiation of thyroxine treatment. Another twenty-one patients (16.6%) were not on thyroxine therapy since surgery. Serum thyroglobulin was assessed on 20.6% (n=26). WBS done using 3-4 mCi liquid radioiodine showed residual functioning thyroid tissues in 41% (n=52). Lymph nodes or bone metastases were detected in 16% (n=21). Of 52 patients with residual thyroid tissues, fourteen patients (30%) received residual ablation dose of 30 mCi of radioiodine. All 21 patients who exhibit abnormal WBS were referred to the cancer unit for high dose therapy. This study showed DTC is more common in young females than in males and Papillary carcinoma is the commonest histological type in Sri Lanka. Though the preferred surgical management is TT or NTT (92%) this study showed inadequacy of excision. In Sri Lanka we have very few experienced thyroid surgeons. Inadequate surgical excision could be due to inexperience and lack of facilities for surgical management in peripheral hospitals. Inadequate surgical excision will directly interfere with the long-term follow up of DTC. Presence of remnant thyroid tissues makes detection and treatment of nodal or distant metastases difficult. High TSH levels necessary to enhance tumor I131uptake and assessment of Tg levels, the most sensitive test for detection of recurrences cannot be achieved with a large thyroid remnants. This results indicative of low sensitivity of the WBS and serum Tg measurements in our set up. We have detected 16% of patients with distant metastases but the actual number may be higher than this figure. Monitoring with Tg is grossly inadequate. Serum Tg test is expensive in our set up prevent us using this facility. Approximately 2/3 of this study group were not received residual ablation partly due to unawareness, not enough radioiodine in the government hospitals and poor follow up in our set up. Management of DTC is still debatable. There is no agreement on extent of surgery, optimal time for WBS, residual ablation and long-term fallow up. Today highly effective method of treatment for DTC is the combination of thyroid surgery (TT/NTT) followed by RAI residual ablation and thyroxine suppression therapy. 30 mCi of radioiodine is the highest permissible activity for out patient treatment according to the local Atomic Energy Agency, Sri Lanka. We prefer to use 30 mCi RAI for residual ablation as it can be used effectively on an out patients basis with associated low cost, convenience and low whole body radiation absorbed dose to the patient.Review of current practice in time to time is justified. Several deficiencies in the management of DTC as a whole were identified. Extent of surgery, radioiodine residual ablation, TSH suppression after surgery and monitoring with serum Tg are grossly inadequate. Guidelines should be introduced to promote the cost effective use of Nuclear Medicine facilities in the management of DTC. Locally agreed protocols are needed to minimize these deficiencies and uplift the existing facilities in the diagnosis, treatment and follow up of DTC patients in Sri Lanka.


098-THAFirst Experiences in 90Y-Zevalin For Treatment of Non-Hodgkin's Lymphoma in ThailandSaesow N et al.Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok, THAILAND-10330

099-UKPathophysiology and non-radionuclide therapy of neuroendocrine tumoursBuscombe JRoyal Free Hospital, Dept. of Nuclear Medicine, Pond Street, Hampstead, London NW3 2QG, United Kingdom

00-UKProblems with antibody treatment of solid tumoursBuscombe JRoyal Free Hospital, Dept. of Nuclear Medicine, Pond Street, Hampstead, London NW3 2QG, United Kingdom

101-UKUse of I-131 Lipiodol for the treatment of liver cancer:A ReviewBuscombe JRoyal Free Hospital, Dept. of Nuclear Medicine, Pond Street, Hampstead, London NW3 2QG, United Kingdom

102-UKUse of Y-90 lanreotide and Y-90 microsheres in treatment of liver tumoursAl-Nahhas A et alDepartment of Nuclear Medicine, Hammersmith Hospital, Du Cane Road, London WI3 0HS, UK

103-UKRadiolabelled Aptamers for Tumour Imaging and Therapy

1 2Perkins AC , Missailidis S 1Dept of Medical Physics, Medical School, University Hospital,

2Nottingham, NG7 2UH; Dept of Chemistry, The Open University, Walton Hall, Milton Keynes, MK7 6AA, UK


1




The growth in biotechnology has led to new techniques for the design, selection and production of ligands capable of molecular recognition. One promising approach is the production of specific receptor binding molecules based on specific nucleic acid sequences that are capable of recognising a wide array of target molecules. These oligonuclide ligands are known as aptamers (1.2). The technology that allows production of aptamer molecules is known as systematic evolution of ligands by exponential enrichment (SELEX). We have used combinatorial chemistry techniques coupled with polymerase chain reaction (PCR) to rapidly select aptamers from degenerate libraries that bind with high affinity and specificity to the protein core of the MUC1 antigen, a tumour marker previously extensively used in tumour imaging and therapy. MUC1 is widely expressed by

normal glandular epithelial cells, however this expression is dramatically increased when the cells become malignant. This has been well documented for breast and ovarian cancer, as well as some lung, pancreatic and prostate cancers (3). Recently it has also been shown that MUC1 is a valuable marker for bladder and has been used for the imaging and targeted therapy of bladder cancer.The aptamer selection process was performed on affinity

S-55



chromatography matrices. After ten rounds of selection and amplification, aptamers were cloned and sequenced. Post SELEX amino modifications have been used to confer nuclease resistance and coupling potential. The aptamers bound to MUC1 antigen with a Kd of 5nm and high specificity, demonstrated by fluorescent microscopy on MUC1-expresing tumour cells. Using peptide coupling reactions, we have successfully attached chelators for Tc-99m radiolabelling. Two of the constructs tested were based on mono-aptamer chelator complexes, one with commercially available MAG3 and one with a novel designed cyclen-based chelator. The other two constructs were based on the use of multi-aptamer complexes, where four aptamers were attached to the four arms of either DOTA or carboxy-porphyrin. The four complexes were labelled with Tc-99m and tested for their efficacy as tumour imaging agents. All four complexes demonstrated specificity for the tumour, due to their MUC1 specificity, at various levels. Biodistribution studies were carried out in mice with MCF7 xenografts. The monomeric aptamer complexes had rapid renal clearance from the system, due to their small size (MW of 8,000 Da). More than 90% of the aptamer based radiopharmaceutical was cleared from the system within the first 15 minutes. To increase retention time, additional constructs based on the design of a tetra-aptamer complex were prepared. A core chelator, such as DOTA and carboxy-porphyrin has been used as a skeleton for the building of multiaptamer constructs aiming to increase the molecular weight of the complex and potentially its stability of binding due to interactions with more than one MUC1 molecules at the surface of the tumour cell. The increase of the MW to 32,000 Da allowed increased retention times in the system, without compromising the exceptional tumour penetration exhibited by all the aptamer based constructs under study. The development of aptamers as small building blocks for targeting agents offers several advantages. These molecules penetrate tumour more readily than whole antibodies, reach peak levels in the tumour more rapidly and clear from the body faster, thereby reducing toxicity to healthy tissues. Our strategy is to manipulate the molecular weight of the construct utilising previously devised methodologies to achieve various polymeric aptamer complexes in order to acieve the optimum balance between the low immunogenicity and excellent tumour penetration. In this way we aim to achieive a balance against the rapid renal clearance that leads to premature elimination of the complex from the system and adequate tumour uptake for diagnostic imaging and targeted therapy. We intend to undertake further work using Re-188 to produce a therapeutic aptamer conjugate.

References:1. Jayasena S. D. Aptamers: an emerging class of molecules that

rival antibodies in diagnosis. Clin. Chem. 1999; 45:1628-1650.2. Guhlke S., Famulok M., Biersack H. J. Aptamers: A novel class

of radiopharmaceutical with diagnostic and therapeutic potential. Eur. J. Nucl. Med. Mol. Imaging. 2003; 30:1441-1443.

3. Zotter S, Hageman PC, Lossnitzer A, Mooi WJ, Hilgers J. Tissue and tumor distribution of human polymorphic epithelial mucin. Cancer Rev 1988;11-12:55-101

104-UKC595 Antibody: A potential vector for targeted alpha therapy

1 2Perkins AC , Allen BJ 1Dept of Medical Physics, Medical School, University Hospital, Nottingham, NG7 2UH, UK

2Center for Experimental Radiation Oncology, Cancer Care Center, St George Hospital, Gray St, Kogarah 2217, NSW, Australia Mucins are high molecular-weight heavily glycosylated glycoproteins with many oligosaccharide side-chains, linked to a

protein backbone called apomucin. A total of 19 different mucin genes (MUC1-MUC4, MUC5B, MUC5AC, MUC6-MUC18) have been identified to date. Mucins are present on the surface of most epithelial cells and play a role in their protection and lubrication. In cancer cells the mucin molecule becomes altered, thus representing an important target for diagnosis and therapy. Urinary epithelial mucin1 (MUC1) is found to be frequently upregulated and abnormally glycosylated in a number of common malignancies, including breast, bladder, colon, ovarian and gastric cancer. The monoclonal antibody C595 is an IgG3 murine MAb raised against the protein core of human MUC1 (1). Epitope mapping has shown that C595 recognizes a tetrapeptide motif (RPAP) within the protein core of MUC1 mucin that contains a large domain of multiples of a highly conserved 20-amino-acid-repeat sequence (PDTRPAPGSTAPPAHGVTSA). This antibody has previously

99m 111been radiolabelled with Tc and In and used for imaging a range of tumour types including ovary, breast and bladder. The antibody

67 188has also been radiolabelled with Cu and Re for the therapy of superficial bladder cancer.More recently we have investigated the pre-clinical use of the

213C595 antibody for targeted alpha therapy using Bi which emits alpha particles with high linear energy transfer (LET), short range ( 80 m) radiation and has a short physical half-life of 45.6 minutes. Alpha particles are some 7300 times heavier than beta particles and in theory, following binding of an alpha immunocongugates to the target, a large fraction of the alpha particle energy is delivered to cancer cells, with minimal concomitant radiation of normal

213 225 213tissues. Bi was produced from the Ac/ Bi generator. For antibody conjugation the chelator, cyclic diethylene- triaminepentacetic acid anhydride (DTPA) was used. Initial experimental studies have concentrated on the targeted therapy of carcinoma of the prostate, pancreas and ovary.On 120 paraffin embedded specimens from patients who underwent radical retro-pubic prostatectomy or trans-urethral-resection of the prostate for primary untreated carcinoma of the pancreas MUC1 expression was detected in 58% primary Ca protate tissues and 90% lymph node metastases but not in normal

213prostates or benign tissues. The Bi-C595 conjugate demonstrated cell killing in PC-3 and DU 145 cell lines isolated from human prostatic adenocarcinoma (2). Other results indicate

213that Bi-C595 targeting efficacy is in accordance with the expression of MUC1 in three pancreatic cancer cell clusters CFPAC-1, PANC-1 and CAPAN-1 and demonstrated effective toxicity of tumour spheroids of up to 100 m in diameter. When administered to tumour bearing mice at 333 MBq/kg the c595 alpha conjugate caused significant tumour growth delay, compared with the non-specific control at after 16 weeks (3). Similar results have been obtained in monolayers and cell clusters of the ovarian OVCAR-3 cell line.We believe this antibody conjugate offers great potential for targeted alpha therapy of prostatic, pancreatic and ovarian tumours.

References:1. Price MR, Pugh JA, Hudecz F, Griffiths W, Jacobs E, Symonds

IM, Clarke AJ, Chan WC, Baldwin RWA monoclonal antibody

S-56



against the protein core of human urinary epithelial mucin commonly expressed in breast carcinomas. Br J Cancer 1990;61: 681-686.

2. Li Y, Rizvi MA, Blair JM, Cozzi PJ, Qu CF, Ow KT, Tam PN, Perkins AC, Russell PJ, Allan BJ. Antigenic expression of human metatstic prostate cancer cell lines for in vitro multiple-

213targeted a-therapy with Bi-conjugates. Int J Radiat Oncol Biol Phys. 2004;60:896-908.

3. Qu CF, Song YJ, Rizvi SMA, Smith R, Perkins AC, A Morgenstern A, Brechbiel, M, Allen BJ. In Vivo and In Vitro Inhibition of Pancreatic Cancer Growth by Targeted Alpha

213Therapy using Bi-CHX.A"-C595. Cancer Biol, Ther. In Press 2005.


The aim of this study was an evaluation of salivary gland function after radioiodine therapy (RIT) in patients with differentiated thyroid cancer (DTC) using sialoscintigraphy with Tc-99m pertechnetate. We investigated 97 patients with thyroid cancer aged from 35 to 65 years. The patients were divided into two groups. First group consisted of 30 patients after total or subtotal thyroidectomy without RIT and symptoms of functional activity changes of salivary glands. Second group included 67 patients after thyroidectomy and following RIT. Administered therapeutic activities varied ranging from 1100 to 4720 MBq. We performed sialoscintigraphy in dynamic mode over a period of 30 minutes (1 frame per 20 sec) with stimulation of gland function at 20 min of study using lemon juice. For evaluation of salivary gland function we used wide spectrum of indices and activity-time curves obtained from zones of interest “salivary glands”. From among the large number of indices determined in the study we could identify three most informative indices. These are 1. Coefficient of concentration (Cc), coefficient of excretion (Ce) and T-max. The mean values of all of these indices were significantly decreased in the patients belonging to the second group in comparison with first group. These are outlined in the following table: Overall significant decrease in salivary gland function was

105-UKRadionuclide Therapy Of Hyperthyroidism: An Over ViewVinjamuri S et alRoyal Liverpool University Hospital, Department of Nuclear Medicine, Prescot StreetLiverpool L78XP, UK


106-UKRadioimmunotherapy of Pancreatic Cancer with Monoclonal AntibodiesVinjamuri S et alRoyal Liverpool University Hospital, Department of Nuclear Medicine, Prescot StreetLiverpool L78XP, UK

107-UKRSialoscintigraphy With Tc-99m Pertechnetate In The Evaluation Of Salivary Gland Function In Patients With Differentiated Thyroid Cancer After Radioiodine TherapyKorol PInstitute of Oncology, Academy of Medical Sciences of Ukraine, Kiev, Ukraine.

detected (P < 0.05) following radioiodine therapy as compared to the control group.

True polycythemia (Vaquez' disease) is the disease of the hemopoietic system of an unknown origin accompanied by increase of erythrocyte count in the peripheral blood with absolute and relative increase in the mass of circulating erythrocytes.True polycythemia is treated with bloodletting and myelosuppressing drugs. This treatment is not always effective. A special place among myelo-depressants is occupied by P-32. Its main therapeutic effect is mediated by the participation in the metabolic processes. Besides DNA damage with beta-radiation, P-32 incorporation by DNA followed by decay and transformation to a stable sulphur isotope (S-32) results in the damage of the structure of nucleic acids, which is main mechanism of cellular proliferation inhibition. Therefore, P-32 is considered a powerful myelosuppressive agent.The indication to P-32 administration is true polycythemia, which, in contrast to secondary polycythemia accompanying numerous diseases, requires special cytostatic treatment.The study involved 152 patients with true polycythemia (76 men and 76 women aged 48) treated with P-32. The treatment was administered in case when bloodletting proved to be ineffective and hematocrit level exceeded 75%. P-32 was administered orally in 100 ml of 10% glucose solution on an empty stomach at a dose of 37-111 MBq with a 4-10-day intervals (mean 6 days). The blood count was checked for 12 weeks. If the number of thrombocytes and leukocytes decreased less than by 25% and the level of hematocrit did not normalize, repeated P-32 treatments were performed.In 13 (8.6%) patients, haematocrit parameters became normal after a single P-32 administration, in 15 (9.9%) patients two treatments with P-32 were necessary to normalize the blood count. In 134 (88.1%) cases P-32 treatment was administered more then two times (maximum 10 treatments). Total P-32 activity ranged from 37 to 740 MBq. Of all the patients who were administered P-32 treatment, hematological remission was achieved in 102 (67%). In these patients, the general condition improved, angina and thrombophlebitis course became more favorable, and ability

108-UKRRadionuclide Therapy for True PolycythemiaAfanasieva NI, Grushka GV, Vasiliev L Ya Department of Nuclear Medicine, Grigor'ev Institute of Medical Radiology, Kharkiv, Ukraine

Indices Parotid GlandRight Left

Gr-I Gr-II P Gr-I Gr-II PCc 2.7± 1.4± 0.04 1.7± 1.3± 0.03

0.8 0.2 0.6 0.2Ce 44.9± 33.1± 0.01 43.6± 28.6± 0.01

2.0 4.0 3.1 5.3Tmax, 14.7± 9.3± 0.0043 14.1± 8.8± 0.004min 1.0 1.5 1.0 1.5

Submandibular glandCc 1.4± 1.2± 0.04 1.4± 1.2± 0.008

0.4 0.5 0.4 0.5Ce 32.5± 22.1± 0.0009 31.5± 22.8± 0.016

2.0 2.3 2.6 2.6Tmax, 12.7± 8.4± 0.015 12.4± 8.8± 0.037min 1.3 1.2 1.2 1.3

S-57



to work improved. Mean remission duration after the first course of treatment with P-32 was 42 months and 26 months after two courses. Mean life span made up 9.3 years.Thus, radionuclide therapy for true polycythemia with P-32 improves the quality of life and increases mean life span in the patients.

Primary treatment for thyroid carcinoma depends on the process dissemination and disease prognosis. The former includes 1) surgery, which is the first and chief method of treatment almost in all cases; 2) I-131 natrium iodide treatment following surgery to achieve ablasticity of the residual tumor tissue, which is especially in some cases; 4) inhibiting hormone therapy is important, if unfavorable prognostic factors are present; 3) distant radiation therapy is possible. The criteria for determining the volume of surgery are the size, morphology, character and rate of growth of the tumor, presence of regional metastases and their mobility, age of the patient, signs of invasion to the adjacent organs. From oncology perspective, minimum volume of intervention in tumors > 2 cm is extrafascial hemistrumectomy, when the tumor is located in the lateral portions; extrafascial hemistrumectomy with removal of the isthmus and resection of the adjacent 1/3 of the neighboring tumor tissue, when the tumor is located in the center and medial portions of the lobe or in the isthmus.Thyroidectomy is a method of choice in large tumors. This allows avoiding development of bilateral cancer, local relapses as well as improving survival and reducing the death rate. Thyroidectomy facilitates I-131 treatment and increases sensitivity of radionuclide body scan with the use of I-131. Diagnostic determining of thyroglobulin for revealing the tumor metastases is possible only after thyroidectomy.Treatment with I-131 sodium iodide is the second essential stage of multimodality treatment for thyroid carcinoma. Multifocal differentiated cancer is found in 20-30% of the patients; residual thyroid tissue, the source of thyroglobulin, reduces informativity of the tumor marker determining; the residual thyroid tissue, as a rule, competes with the relapses and metastases of thyroid cancer for I-131 absorption; hidden distant metastases of thyroid carcinoma can be revealed by I-131 scan only on complete ablation of the residual thyroid tissue. All these prove for I-131 treatment with the purpose of ablation of the residual tumor tissue.In the post-operative period, I-131 treatment is indicated in case of non-radical surgery, or when the radical charter of the surgery is doubtful. The advantages of this approach have been demonstrated by the reduction in the incidence of relapses and increase of the life span.According to the international experience and the standard treatment protocols for differentiated thyroid cancer, planned distant gamma-therapy (DGT) is considered unexpedient due to low sensitivity of the tumor tissue. DGT can be indicated in case of incomplete or doubtful surgery, especially in elderly patients with poorly differentiated tumor, in case, when the tumor is poorly differentiated and I-131 absorption is inconsiderable or completely absent. In case when surgery is not possible due to the

109-UKRUp-to-Date Program of Treatment and Long-Term Follow-up of the Patients with Differentiated Thyroid CarcinomaAfanasieva NI, Grushka GV, Astapieva OM Department of Nuclear Medicine, Grigor'ev Institute of Medical Radiology, Kharkiv, Ukraine

tumor process dissemination, DGT can stabilize the tumor growth. On the other hand, DGT is not indicated in case of radical surgery or in children, even with an extended tumor process. In this case, the protocol of treatment includes surgery followed by I-131 therapy. External irradiation should not be performed, if a pronounced therapeutic effect is not expected. In other words, gamma-therapy is advisable only when surgery and I-131 treatment have proven to be ineffective.The purpose of a long-term follow-up is revealing locoregional relapses and distant metastases. The patient examination is based on combined use of clinical examination, echography of the neck region, thyroglobulin (Tg) level assessment in the blood serum, whole body scan with residual activities using I-131 natrium iodide. Increased Tg level is considered to be the only sign of thyroid cancer metastases in the operated patients, even when the findings of clinical, x-ray and scintigraphic studies are negative.Comparison of sensitivity of diagnostic scintigraphy with I-131, sonography of the neck and assessment of Tg level in the operated patients after radioiodine ablation of the residual thyroid tissue suggests that laboratory study of Tg level correlates with the clinical state of the patients and the findings of isotopic techniques in 99.5% of the patients.During dynamic observation it is necessary to control TSH level for adequate hormone therapy with the purpose of inhibiting thyrotropin secretion to prevent relapses and metastases of the thyroid tumor.

Distant metastases of thyroid carcinoma (TC) occur due to dissemination of cancer cells through the lymph and blood vessels. They develop in 10-15% of patients with differentiated thyroid carcinoma and are the main cause of death in cancer patients. Appearance of distant metastases depends on a number of factors, i.e. the age of the patients (chiefly in children and those over 45); small size tumors; invasive growth of the tumor outside the thyroid capsule; involvement of the sentinel lymph nodes; poor differentiation of the tumor; incomplete surgical removal of the tumor.Distant metastases mainly localize in the lungs and/or bones. In thyroid cancer patients with suspected bone metastases the latter are revealed radiologically on the primary examination (approximately in 95.9% of cases). In 25% of them, they are seen at body scan with I-131 on residual activities. Probability of visualization of iodine-positive bone metastases is higher at ablation of residual thyroid tissue. When the metastases are revealed by x-ray study, they cannot be treated using I-131, which emphasizes the necessity of other methods of treatment: surgery and distant radiation therapy. But due to multiple character of bone metastases surgery for these metastases is impossible. Within the period of 1999-2004 we studied 310 patients with differentiated TC aged 22-72 (of them 254 women and 56 men). Bone metastases were revealed in 15 (4.8%) patients, of them 13 women and 2 men aged 46-68. As to the stage of the tumor with bone metastases, the patients were grouped as follows: T N M -1 1 0 0

(6.7%), T N M -1 (6.7%), TxNxMo-4 (26.7%), T N -1M -9 2-3 0 0 1-4 0 1

(60%) patients.

110-UKRCombination Radiation Therapy for Bone Metastases in Thyroid CancerAfanasieva NI, Grushka GV, Muzhychuk OV, Astapieva OM Department of Nuclear Medicine, Grigor'ev Institute of Medical Radiology, Kharkiv, Ukraine

S-58



Of the 15 patients with bone metastases, papillary cancer was verified in 5 (33.3%) patients, follicular in 5 (33.3%) papillary cancer follicular variant in 1 (6.7%), medullary in 4 (26.3%). Together with bone metastases, 5 (33.3%) had metastases to the lung parenchyma, diffuse and solitary; 12 (80%) had metastases to sentinel and distant lymph nodes.The presence of bone metastases was revealed using x-ray study and confirmed using bone scan with Tc-99m pyrophosphate. During the treatment the patients with bone metastases were administered 1480-14,134 MBq of I-131. Of all patients with bone metastases, bone metastases accumulated I-131 only in 4 (19%) patients. Thus, treatment of TC with bone metastases only with I-131 did not produce a desirable palliative effect as well as did not control the progress of metastasizing. Therefore, together with I-131 treatment the patients received P-32 (sodium phosphate) treatment. P-32 treatment was started not earlier then 4 months after treatment with I-131. P-32 was administered orally in 100 ml of 10% glucose solution on an empty stomach, 74-120 MBq pert treatment with 4-7- day intervals. Total P-32 activity during one course of treatment made up 296-444 Mbq.Combination radionuclide therapy with I-131 sodium iodide and P-32 sodium phosphate was given to 4 patients with papillary and follicular TC with bone metastases which did not accumulate I-131. Two of these patients had diffuse metastases to the lung parenchyma. The patients received 305-369 MBq of P-32. The radiation load on the red bone marrow was 1098-1328.4 mSv at oral P-32 administration that on the body was 823.5-996.3 mSv. The signs of myelosuppression were not observed during the stay at the Institute. One patient had insignificant reduction of thrombocyte level up to 91.0 x 109 /l and leukocyte level to 2,4 õ 109/l 2 month after the treatment. Three months after systemic radionucl ide therapy the s igns of inconsiderable myelosuppression disappeared.Pain syndrome disappeared 5-12 days after combination systemic radionuclide therapy, and the patients were able to care for themselves. Flare phenomenon was not seen. A positive feature of combination radionuclide therapy with I-131 sodium iodide and P-32 sodium phosphate together with treatment of bone metastases is possibility continue the treatment of metastases to the sentinel lymph nodes and lung parenchyma, which often accompany bone metastases. Observation of the patients for a year demonstrated that all the patients, which had received combination radionuclide therapy, were alive, pain syndrome was absent in two, in two this was moderate but better then the pain before the beginning of the treatment. All patients did not accumulate I-131 sodium iodide in the lymph nodes.Combination systemic radionuclide therapy with I-131 sodium iodide and P-32 sodium phosphate in TC with metastases to the bones is a method of choice and allows performing adequate treatment of the patients with a continuing process in the thyroid with metastatic involvement of the sentinel lymph nodes and lung parenchyma.

111-URU188Intravascular Radiation Therapy with Liquid-Filled Re

Balloon Catheter: Results of an International Atomic Energy Agency (IAEA) Multicentre Study

1 2 2 3 4Alonso O , Chae I-H , Chung JK , Gutierrez C , Kropp J , Önsel 5 6 7 8 9 10C , Peix A , Plonska E , Szilvasi I , Knapp FF , Padhy AK , Storto 10 10G , Dondi M.

1Nuclear Medicine Centre, University of Uruguay, Montevideo; 2Uruguay, Seoul National University Hospital, Seoul, Republic of

3Korea; Fundación Cardioinfantil, Bogotá, Colombia.

112-USATherapeutic Applications of Rhenium-188 in Nuclear Medicine and Oncology - Current Status and Expected Future PerspectivesKnapp Jr. F. F. (Russ)Nuclear Medicine Program, Isotope Development Group, Oak Ridge National Laboratory (ORNL), Oak Ridge, TN, USA

4Technische Universitaet Dresden, Dresden, Germany; 5 6Cerrahpasa Medical Faculty, Istanbul, Turkey; Instituto de Cardiología y Cirugía Cardiovascular, Havana, Cuba; 7Pomeranian Academy of Medicine, Szczecin, Poland; 8 9Semmelweis University of Medicine, Budapest, Hungary; Oak

10Ridge National Lab, Oak Ridge, TN, USA; Division of Human Health, Nuclear Medicine Section, IAEA, Vienna, Austria.Intravascular radiation therapy (IVRT) using a standard

188angioplasty balloon filled with Re-perrhenate has been shown to reduce the risk of restenosis after PTCA. This strategy can constitute a cost-effective, self-centering approach. The purpose of the present study was to evaluate the safety and effectiveness of this technique in the framework of a prospective, multi-center and multinational co-ordinated research project conducted by the IAEA. One hundred and eleven patients from 7 participating countries, with a mean age of 60 years (range: 36-81), with de novo (n=47) or in-stent restenosis (n=64) and proven ischemia were included. After successful PTCA with (n=24) or without (n=87) additional stent implantation a second standard balloon

188was placed into the PTCA area and filled with Re-perrhenate. Irradiation time was 405 ± 169 sec to achieve a dose of 18 Gy at 1 mm depth from luminal surface. Six month angiographic and clinical follow-up was available in 85 patients. Results were compared with those obtained from a control group (n=62).Clinical and procedural data did not differ between the groups except a higher rate of de novo lesions in the control group (62%)

188compared with the Re group (41%, p=0.0016). Binary restenosis rates were significantly lower at the target lesion after brachytherapy compared with the control group (30% versus 40%, p=0.049). Target vessel revascularization rate did not differ between both groups (8.1% versus 5.9% for the control and treated group, respectively, p=0.74). Besides, late thrombosis was only

188developed in the Re group (n=3), with subsequent myocardial infarction. An additional stent had been implanted in two of them.

188IVRT using Re liquid-filled balloons is a feasible and effective therapeutic modality for decreasing the incidence of restenosis following PTCA. Additional stenting after brachytherapy should be discouraged. Long term follow-up studies are needed to evaluate the clinical benefit of the procedure.

The increasing use of unsealed radioactive targeting agents for cancer treatment requires the routine availability of cost-effective radioisotopes. Rhenium-188 (Re-188; half-life 16.9 hours) is a high-energy beta-emitter (E 2.12 MeV), readily available no-max

carrier-added from the alumina-based tungsten-188 (half-life 69 days)/rhenium-188 generator system [1]. Rhenium-188 also emits a 155 keV (15%) gamma photon, permitting gamma camera imaging for biodistribution and dosimetry evaluation. The versatile chemistry of rhenium allows attachment to a wide variety of targeting molecules for Re-188 applications in nuclear oncology for both palliative metastatic treatment and targeted tumor therapy - radionuclide synovectomy, and coronary restenosis therapy. The long parent half-life and consistent

S-59



performance provide an indefinite generator shelf-life of several months with high Re-188 elution yields (75-85 %) and

-6consistently low W-188 parent breakthrough (< 10 ) [1]. Simple post-elution concentration methods have been developed which provide very high specific volume solution of Re-188 for radiolabeling ( > 700 mCi/mL saline/1 Ci generator) [1]. Over 60 physician-sponsored clinical trials are currently in progress worldwide with applications in nuclear medicine, nuclear oncology and interventional cardiology.A variety of Re-188-labeled therapeutic radiopharmaceuticals and devices are being developed for clinical trials currently in progress for treatment of both benign and metastatic oncological disorders. Palliation of metastatic bone pain with Re-188-HEDP - prepared from a simple “kit” - has been demonstrated as a cost-effective alternative to similar agents [2-4]. Recent studies have in fact demonstrated the enhancement of progression-free interval and survival time by repeated Re-188-HEDP injections to patients with metastatic disease from prostate cancer [2]. The use of the Re-188-labeled antiNCA95 (CD66) antibody in conjunction with external beam irradiation is an effective method for myeloablation/conditioning prior to stem cell transplantation in leukemia patients [5]. Rhenium-188-labeled peptides are also being developed and evaluated for targeted therapy. The Re-188-P2045 SST2/SST5-binding peptide is being developed for the treatment of small cell/non small cell lung tumors and the initial results of a Phase I trial have been reported [6]. The submitted manuscript has been authored by a contractor of the U.S. Government under contract DE-AC05-00OR22725. Accordingly, the U.S. Government retains a nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for U.S. Government purposes.Therapy of refractory liver cancer is being explored by site-specific trans-arterial delivery of the Re-188-labeled HDD- [7] and DEDC-Lipiodol [8] conjugates in several countries, including an IAEA-sponsored multi-center trial [9]. Use of Re-188-B20 albumin particles has also been reported as an effective alternative approach for the treatment of metastatic liver cancer therapy [10]. Although the use of radioactive stents for inhibition of restenosis following coronary angioplasty has been eclipsed at most centers with the use of growth inhibitor-coated stents, the use of Re-188 liquid-filled balloons for this application has played an important role in developing and demonstrating the cost-effective usefulness of preventing coronary restenosis with beta-emitting radioisotopes and still represents a cost-effective alternative for restenosis therapy when cost is an issue.The tungsten-188/rhenium-188 generator represents a convenient and cost-effective system to provide high specific activity rhenium-188 for a wide variety of therapeutic applications. In developing countries the tungsten-188/rhenium-188 generator is of particular importance because of its indefinite useful shelf-life and rhenium-188 represents one of the few therapeutic radioisotopes that can be cost effectively routinely available. Use of the tungsten-188/rhenium-188 generator in a centralized radiopharmacy would be expected to optimize the costs for broader use of Re-188 in nuclear oncology. This talk will focus on discussion of the clinical applications of Re-188 in nuclear oncology and the expected expanding role of this therapeutic radioisotope for radionuclide therapy.Acknowledgement: Research at the Oak Ridge National Laboratory (ORNL) supported by the U.S. Department of Energy (DOE) the under contract DE-AC05-00OR22725 with UT-Battelle, LLC.

References

1. Knapp FF Jr. “Rhenium-188 - A Generator-Derived Radioisotope for Cancer Therapy,” Cancer Biotherapy and Radiopharm 1998; 13: 337-349

2. Palmedo H, Manka-Waluch A, Albers P et al. Repeated Bone Targeted Therapy for Hormone-Refractory Prostate Carcinoma: Randomized Phase II Trial with the New, High-Energy Radiopharmaceutical Rhenium-188-HEDP. J Clin Oncol 203; 21: 2869-2875

3. Liepe K, Kropp J, Runge R et al. Therapeutic Efficacy of Rhehium-188-HEDP in Human Prostate Cancer Skeletal Metastases. Brit. J Cancer 2003; 89: 625-629

4. Savio E, Gaudiano J, Robles A et al. Rhenium-188-HEDP: Pharmacokinetic Characterization in Osseous Metastatic Patients with Two Levels of Radiopharmaceutial Dose. BMC Nucl. Med 2001; 1(23): 471-1485

1885. Bunjes D. Re-Labeled anti-CD66 Monoclonal Antibody in Stem Cell Transplantation for Patients with High-Risk Acute Myeloid Leukemia. Leuk Lymphoma 2002; 43: 2125-2131

6. Bugaj JE, Bickel EM, Azure MT et al. Radiotherapeutic 188Efficacy of a SSTR-Targeting Peptide ( Re-P2045) in a

Small Cell Lung Cancer (SCLC) Mouse Model. J Nucl Med 2002; 43: 123P (Abstract).

1887. Paeng JC, Jeong JM, Yoon et al. Lipiodol Solution of Re -HDD as a New Therapeutic Agent for Transhepatic Arterial Embolization in Liver Cancer: Preclinical Study in a Rabbit Liver Cancer Model. J Nucl Med 2003; 44: 2033-2038

8. Duatti A, Martindale AA, Turner JH et al. Rhenium-188 Lipiodol Kit Formulation for Therapy of Hepatocellular Carcinoma (HCC). World J Nucl Med 2002;1: S180

9. Sundram FX, Yu S, Somanesan S et al. Phase I Study of Transarterial Rhenium-188-HDD Lipiodol in Treatment of Inoperable Primary Hepatocellular Cacinoma - A Multicentre Evaluation. World J. Nucl Med 2002; 1: 5-11

10. Kropp J, Pinbkert J, Wunderlich G et al. Radiochemistry, Evaluation and First Clinical Results in the Treatment of Oncologic Diseases with Rhenium-188-Labeled

thMicrospheres, In, Proceedings, the 11 Mediterranean Symposium on Nuclear Medicine and Radiopharmaceuticals, Athens, Greece, May 28-30; Mediterrea Pub., Athens (ISBN 960-86437-2-4); pp. 157-166 (2003).

Because of localized energy deposition within a very small volume, cellular targeted therapy with high linear energy transfer (LET) Auger-electron and alpha-particle emitting radioisotopes is of great interest. While the energy deposition from alpha particles usually encompasses several cell diameters, the dose from Auger electrons is confined to a single cell. Two major challenges for broader use of Alpha and Auger emitters are the efficient and cost effective routine production of sufficient levels of these radioisotopes, and the availability of targeting molecules to which the radioisotopes can be attached for cellular delivery of sufficient levels of activity for effective therapy. Examples of several Alpha-

113-USATherapy with High LET Radioisotopes: Can Sufficient Levels of Attractive Auger and Alpha Emitters be Produced to Make Their Use Practical ?Knapp, Jr. F.F. (Rush), Mirzadeh S, Stabin M, Brill ABNuclear Medicine Program, Oak Ridge National Laboratory (ORNL), Oak Ridge, TN, Radiology Department, Vanderbilt University, Nashville, TN, USA.

S-60



Figure 1. Reactor production of platinium-195m

Half eV per EnergyRadionuclide Life Comment Emission Transformatio Deposited

s n Gram rad/ Ci--2x 10 h

Accelerator produced (A)/accelerator-produced generator parent

Actinium-225 10 d U-233 Th-229 Ac-

225

Bismuth-213 45.6 From Ac-225 generator 44.2 0.972

mBismuth-212 60.5 From Pb-212 ???? 50.0 1.1

mIndium-111 2.8 d From Cd-111(p,n)In-111 EC 3.45 0.071Neodynium-140 3.37 d From Pr-141(p,2n)Nd- EC 15.6 0.343

140Reactor produced (R)/reactor-produced generator parentPlatinum-195m 4.02 d From Ir-195 decay IT 18.3 0.403

Ir-193(2n, )Ir-195

Rhodium-103m 56.1 From Ru-103 generator IT 3.7 0.081

m Ru-102(n, )Ru-103

Table 1. Examples of High LET Radioisotope of Current Interest for Targeted Therapy

m

® ® a

a

g

g

Reported ProductionRadioisotope Yield Data Reference/CommentActinium-225 From Th-229 decay [2] Th-229 inventory from U-233 is limited (Parent of Ra-226(p,2n)Ac-225

Bismuth-213) Yield = 9.61 Ci/mg Ra-226/h,

15.9 MeV at 50 A current [3]

Neodymium-140 Pr-141(p,2n)Nd-140 [4,5] Estimated production yield

Yield = 800 Ci/ h, 35 MeV

at 15 A current

Platinum-195m Ir-193(2n, )Ir-195? Pt-195m [6,7] Initial tracer level study

Ruthenium-103 Ru-102(2n, )Ru-103m

(Parent of [8]Rhodium-103m)Table 2. Production Yields of Key Examples of High LET Radioisotopes

m

m

m m

m

g

g

S-61



and Auger-emitting radioisotopes of current interest are summarized in Table 1.Alpha- and Auger electron-emitting radioisotopes can be produced in accelerators (A) and nuclear reactors (R), and several alpha emitter congeners (i.e. thorium-229) can be obtained from uranium decay products. The challenge for reactor production, is the availability and exploitation of

methods - other then the usual radiative (n, ) production route which will provide no-carrier-added (nca) or the high specific activity radioisotopes of interest. The submitted manuscript has been authored by a contractor of the U.S. Government under contract DE-AC05-00OR22725. Accordingly, the U.S. Government retains a nonexclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for U.S. Government purposesHigh LET radioisotopes of current interest which are in the initial stages of development and/or which demonstrate practical use in clinical trials include several alpha-emitters, in particular bismuth-213 - and also the actinium-225 parent - astatine-211 and bismuth-212. Extensive experimental studies have been reported with Auger iododeoxyuridine (IdUR) radiolabeled with the iodine-125 emitter-labeled [1]. However, development of production and processing technologies, radiolabeling and intracellular targeting studies, and experimental evaluation of the subsequent therapeutic potential of other Auger emitters is only in its infancy. Examples of Auger-emitters of current interest include indium-111 (A), neodymium-140 (A), platinum-195m (R) and rhodium-103m (R production of ruthenium-103 parent) (Table 1).One Auger-electron emitter of particular interest is platinum-195m [9], which has been previously available in only low specific activity (approx. 1 mCi/mg). Demonstration of a new indirect production route via decay of reactor-produced iridium-195 (Figure 2), indicates that this Auger emitter may now be available in significantly higher specific activity (> 70-100 mCi/mg) which will now permit for the first time studies of the therapeutic potential of this Auger emitter.Because of recent success in peptide targeting to membrane-based cellular receptors which are often over-expressed in tumor cells and advances in radiolabeling chemistry and radioisotope production and processing technologies, intracellular targeted therapy with Alpha and Auger emitters has taken on a new dimension. This talk will review the issues associated with the production and processing of several key candidates and the possibility of producing sufficient levels required for sustained research efforts and clinical trials.Acknowledgement: Research at the Oak Ridge National Laboratory (ORNL) supported by the U.S. Department of Energy (DOE) the under contract DE-AC05-00OR22725 with UT-Battelle, LLC.

References1. Kassis AI. The Amazing World of Auger Electrons. Int. J.

Radiation Biol 2004;80: 789-8032. Boll RA, MalkemusD, Mirzadeh S. Production of

Act in ium-225 for Alpha Par t ic le Media ted Radioimmunotherapy, Appl Radiat Isot 2005; 62: 447-679

3. Apostolidis C, Molinert R, McGinley et al. Cyclotron Production of Ac-225 for Targeted Alpha Therapy, Appl Radiat Isot 2005; 62: 383-387

4. Roesch F, Brockmann J, Lebedev A et al. Production and

g

Radiochemical Separation of the Auger Electron Emitter 140Nd. Acta Oncologica 2000; 39: 727-730

5. Yakushev EA, Kovalik A, Filosofov DV et al. An Experimental Comparison of the K- and L-Auger Electron

140 111Spectra Generator in the Decays of Nd and In. Appl Radiat Isot, in press (2005)

6. Mirzadeh S, Du M, Beets AL, Knapp FF. High Specific Activity Platinum-195m,“U. S. Patent No. 6,804,319”. Issued October 12, 2004.

7. Knapp FF, Mirzadeh S, Beets AL et al. Production of Therapeutic Radioisotopes in the ORNL High Flux Isotope Reactor for Applications in Nuclear Medicine, Oncology and Interventional Cardiology, J. Radioanalyt Nuc Chem. 2005; 263 (2): 503-509

8. Bernhardt P, Forsell-Aronsson E, Jacobsson E et al. Low Energy Electron Emitters for targeted Therapy f Small Tumors. Acta Oncol 2001; 40(5): 602-608

9. Mariana G, Bodel L, adelstein SJ, Kassis AI. Emerging Roles for Radiometabolic Therapy of Tumors Based on Auger Electron Emission. J Nucl Med 200; 41(9): 1519-1521

Bone-localizing therapeutic radiopharmaceuticals are utilized on the basis of the radionuclide's therapeutic particulate emissions (primarily low to intermediate energy electron emission). The requirements therefore are different from those of bone imaging agents that consist mainly of short-lived single photon emitters. Lately, the therapeutic bone-seeking radiopharmaceuticals have attained increasing importance due to their potential future role in alleviating pain from osseous metastases in cancer patients, for the treatment of joint pain resulting from inflamed synovium (radiosynovectomy) or from various forms of arthritic disease, and for the treatment of primary/metastatic cancer in bone.The interest in application of radionuclides to therapy of bone malignancies, particularly for palliative relief of metastatic bone pain, is not new but has recently undergone a renewal. It had its origin in the earliest days of the nuclear era but fell into relative obscurity for some time, until about two decades ago. Both Sr-89 and P-32 were investigated as early as the 1940's for the treatment of metastatic cancer to bone. Detailed investigations in the seventies and eighties suggested again that Sr-89 would be useful for relief of pain from osseous metastases, thus resulting in the FDA approval for its routine application in 1993. This work also

stimulated further clinical research in order to find other -emitting radionuclides, which may have improved physical properties that permit treatment with fewer side effects on the myeloproliferative cells in the bone marrow. The newer potential radionuclides include the FDA-approved Sm-153, and others still undergoing investigation, e.g., Sn-117m, Lu-177, and Re-186/188, etc. The basis for the action of most of these therapeutic agents is their incorporation into bone mineral and their beta emission, which limits their range of action to the near neighborhood of their increased concentration in pathological areas such as metastases, where the attempt at healing by the bone results in increased uptake. Tin-117m is an exception in that its emission consists primarily of short-range high-LET conversion electrons rather than beta particles, thus considerably reducing the myelotoxic

114-USAFuture Directions in Bone-Localizing Therapeutic Radiopharmaceuticals. Srivastava SC. Medical Department, Brookhaven National Laboratory, Upton, New York, USA.

b

S-62



effects in therapeutic procedures. These same radionuclides also have properties that make them potentially useful for the treatment of bone metastases and of many bone and joint disorders.This paper will briefly review and summarize the available chemical, biopharmacokinetic, and clinical information on the current FDA-approved as well as experimental bone-localizing therapeutic radiopharmaceuticals which have so far been utilized primarily for bone pain palliation. Their potential usefulness for the treatment of: 1) primary/metastatic cancer in bone; 2) joint pain resulting from inflamed synovium including hemophilic arthropathy (radiosynovectomy); 3) rheumatoid arthritis and other rheumatological disorders; and 4) various osteoblastic diseases, will be discussed. Because of its almost ideal therapeutic properties and considerably reduced myelotoxicity, tin-117m appears to have a distinct advantage over other radionuclides and will be discussed in more detail. Work supported by the United States Department of Energy (National Nuclear Security Administration IPP Program, and the Office of Biological and Environmental Research), under Contract #DE-AC02-98CH10886.

Our group has initiated investigations on the use of radiolabeled adenoviral (Ad) sub-unit proteins for delivering suitable radionuclides into tumor cells for molecular imaging as well as for combined gene/radionuclide therapy of cancer. A number of issues involved in developing combined gene/radionuclide delivery into tumors mediated by Ad vectors have been identified and are being addressed. Whereas current clinical trials of gene therapy using Ad vectors involve non-systemic delivery of therapeutic genes, the delivery of radionuclides preferably would involve systemic (i.v.) administration. The distribution and delivery of Ad sub-unit proteins following i.v. administration is not understood and must be studied and optimized. In addition, retention of the selective binding and internalization into tumor cells of the radiolabeled viral vectors remains an unmet challenge. We used the intact adenovirus (Ad, ~80 nm diameter), native adenoviral fiber protein (AdFP, 180 kD trimer, purified from infected human cultured cells) and the adenoviral fiber “knob” protein (recombinant AdFKP, 60 kD, synthesized in E. Coli), all of which interact with the in-vivo cellular receptor, coxsackie and adenovirus receptor (CAR) through the knob domain of the adenovirus fiber protein. Our initial studies were aimed at optimizing the labeling conditions using I-131 and In-111 to maintain CAR binding activity of the radiolabeled preparations. The CAR binding was retained as determined using reaction with biotinylated CAR followed by chemiluminescence detection. The biodistribution results in mice and rats following i.v. administration (autoradiography, tissue counting) showed that all three vectors localized preferentially in CAR-expressing organs (liver, lung, heart, kidney), as expected. The CAR binding of Ad-2 wild serotype was better (~8x stronger) than Ad-12, in particular following radiolabeling.Based on the above results, we further focused on the recombinant knob protein as well as CAR and its variable type domain CAR D1 for more detailed studies. The knob protein can be bioengineered to interact with molecular targets, e.g., tumor-associated antigens,

115-USARadiolabeled Adenoviral Sub-Unit Proteins for Molecular Imaging and Therapeutic Applications in Oncology.Suresh C. Srivastava, Medical Department, Brookhaven National Laboratory, Upton, New York, USA.

using in vitro evolution methods. The optimized iodination procedure was as follows. NaI-131 was incubated with one Iodobead for 5 min in TRIS pH 6.8. The reactive iodine species was then separated from the bead, and the knob protein added to it for 1 minute. This method produced I-131-knob without either SDS-PAGE detectable conformational damage or loss of CAR-binding activity. Following intravenous injection in mice, there was uptake in CAR-binding tissues (liver, kidney, heart, and lung) as expected, but blood and whole body clearance were both quite rapid. When mice were pre-injected with excess unlabeled knob (cold competitor), the level of I-131-knob (% injected dose/g) in blood was increased (19.4 vs. 2.5) with a corresponding decrease in metabolic deiodination (6.5 vs. 33.5 in stomach). Radioiodinated knob mutants, which are devoid of CAR-binding activity showed high levels (% injected dose/g) in blood at 6 h post injection (31.0), whereas wild-type I-131-knob in blood at 6 h had decreased to background levels (2.0). Knob mutants, which are unable to interact with CAR, are retained longer in the blood and have slower metabolism. These preliminary results suggest that engineered ligands based on adenoviral sub-unit proteins (with or without the ability to bind to CAR) may prove useful as a new class of ligands for molecular imaging and possibly for the combined gene/radionuclide therapy of cancer. Work supported by the United States Department of Energy (Office of Biological and Environmental Research, and the NE/Office of Isotope Programs), under Contract #DE-AC02-98CH10886.

At MU, radioisotopes are being developed and evaluated for targeted radiotherapy of cancer. One approach focuses on the lanthanide group of radionuclides. Radiolanthanides share similar chemical properties that allow for attachment to biomolecules utilizing the same chelator, DOTA, but have unique half-lives (dose rates) and beta energies (tissue penetration ranges). In addition they all have a low abundance gamma emissions that allow for imaging and tracking dosimetry. This work has resulted in the approval of Sm-153-EDTMP for the palliation of pain associated with metastatic bone cancer and the investigation of Ho-166-DOTMP for marrow ablation in patients suffering from multiple myeloma. Current efforts have focused on developing high specific activity radioisotopes which can be attached to biomolecules that are taken up selectively by diseased tissues, thus delivering toxic radioactivity to diseased tissue while minimizing or sparing damage to healthy or normal cells. Tumor targeting biomolecules can be radiolabeled with different radioisotopes tailored to treat different cancers.Radiolabeled peptides and antibodies have shown promise for radiotherapy (RIT) of cancer. However, low concentrations of tumor-associated antigens require that biomolecules be radiolabeled with high specific activity radionuclides. Production of radioisotopes by direct neutron capture often results in specific activities that are too low for RIT. Another disadvantage of the direct approach is the production of long-lived impurities such as Lu-177m (half-life = 160 days). An alternative method for producing radioisotopes is via an indirect method: neutron capture followed by beta decay of a parent radioisotope to the

116-USADevelopment and Evaluation of High Specific Activity Radioisotopes for RadiotherapyC.S. Cutler, M.R. Lewis, H.P. Engelbrecht, A.R. KetringUniversity of Missouri Research Reactor Center (MURR), Veterinary Medicine and Surgery, Columbia, MO USA

S-63



desired daughter radionuclide. For example, neutron activation of Nd-148 produces Nd-149 (half-life = 1.7 hr), which is followed by beta decay, producing Pm-149. Indirect methods have been developed at MURR to produce the high specific activity radionuclides Lu-177, Pm-149, and Ho-166. These high specific activity radionuclides with differing nuclear properties have been attached to biomolecules and evaluated for therapeutic efficacy in tumor bearing animals.

A number of chromatographic separations have been evaluated to produce high specific activity radionuclides with mixed results. A variety of parameters were compared such as time of separation, efficiency of separation, ease of operation, and radionuclidic and radiochemical purity of the desired radionuclide. In addition the radiolanthanides produced underwent a ligand titration assay to determine percent incorporation. The radiolanthanides were then attached using DOTA as the chelator to biomolecules of interest. These radionuclides have been attached to somatostatin peptide analogs and antibodies such as CC49 and evaluated for in vitro stability by serum and hydroxyapaptite challenge, receptor binding, and biodistribution in tumor bearing rodents.Although the separations have proven to be achievable they have at times been hindered by the introduction of stray metals requiring development of additional clean-up methods. Upon ICP-MS analysis separations were shown to introduce high levels of Fe, Zn, Ca, Ni, Cu and P. These metals were eliminated through a number of techniques including prewashing the resins, removing all metal and glass components and development of methods to remove the unwanted metals from the desired radiolanthanides. The high specific activity radiolanthanides were complexed in high yields using the DOTA chelator (> 95% intact) and exhibited high stability to both serum and hydroxyapatite challenge (bone mimicer) (>90% intact out to seven days). Receptor binding for these complexes were similar and in the nanomolar range.Complicated high specific activity radiolanthanides can be produced in high radiochemical and radionuclidic purity. Furthermore, due to their similar chemistry they can be attached to peptides and antibodies utilizing the DOTA chelator and demonstrate high stability in vitro and in vivo. Biodistribution results of these radiolanthanides attached to different targeting molecules demonstrate similar in vivo distribution and illustrate that their therapeutic efficacy is determined largely by their half-lives (dose rates) and beta energies (tissue penetration ranges).


117-USAAdvances in targeted radioisotope therapy in cancerDivgi CDivision of Nuclear Medicine, Memorial Sloan Kettering Cancer Centre, New York, USA

118-USAThe role of imaging in planning therapy in cancerDivgi CDivision of Nuclear Medicine, Memorial Sloan Kettering Cancer Centre, New York, USA

119-USAIncorporating FDG PET Imaging in the Response Criteria for Non-Hodgkin's Lymphoma Wiseman GDepartment of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA

120-USARole of Radionuclides in Therapy of Haematologic MalignanciesWiseman GDepartment of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA

121-UZBNuclear Medicine in Uzbekistan & Current status of Radionuclide therapy in the countryRasulova N and Khodjibekova MDepartment of Nuclear Medicine, Clinical Centre for Surgery, Tashkent, Uzbekistan




The population of Uzbekistan is 26 million and to cater to this population we have only two nuclear medicine departments; one at the Clinical Centre for Surgery and the other at the Institute of Endocrinology, both situated in Tashkent, the capital city of Uzbekistan. Over the years through its own initiatives and through the support provided by several International Organizations including the IAEA, Uzbekistan has been able to marginally improve its nuclear medicine services. SPECT imaging was introduced through generous support from IAEA in the year 2001. As a result of this, the country is now able to provide modern in vivo nuclear medicine service to the population in a limited scale. At the Clinical Centre for Surgery we are able to provide gamma camera and SPECT imaging services to patients suffering from various nephro-urological, cardiac, neuro and oncological disorders. The other nuclear medicine centre at the Institute of Endocrinology does not have any modern imaging system. However it has been engaged in providing radionuclide therapy service for thyroid diseases like thyroid cancer and hyperthyroidism. From the year 1983 to 1999 the country has reported a total number of 6374 cases of Thyroid Cancer. This number is growing each year, for example the incidence of thyroid cancer in 1989 was 1.95 per 100,000, which has grown to 2.39 per 100,000 in 1999. While the Institute of Endocrinology provides therapeutic service to thyroid diaseases, the main role of the Nuclear Medicine Department of Republic Specialized Center of Surgery is in following-up of patients after therapy by performing large dose I-131 whole body imaging, screening for metastases and for assessment of results of radioactive iodine therapy.

Isotope Half-Life Max. bEnergy Ave. Range Approximate Range

(days) (MeV) (mm in water) (cell diameters)

Lu 6.65 0.50 0.24 20

Pm 2.21 1.1 0.71 60

Ho 1.12 1.8 1.38 117

Table 1. Nuclear Properties of Radiolanthanides.

S-64



Besides treating thyroid diseases with I-131 limited services are also available for treatment of polycythemia vera rubra with P-32 and radionuclide therapy for metastatic bone pain.Radiionuclide therapy is growing rapidly around the world and to-day it has become one of the most important aspect of nuclear medicine practice. To this effect, there is scope for improving the quality and quantity of radionuclide therapy service in Uzbekistan. Various achievements, problems and requirements for future improvement of facilities in the country will be discussed. It is hoped that our participation in this congress will provide the necessary boost to the specialty in the country and incentives to the practitioners.

In order to assess the efficacy and safety of radiosynoviorthesis we performed clinical evaluation and chromosomal studies in 104 patients treated with a number of radiopharmaceuticals (61 Knees, 26 Elbows, 14 Ankles and 3 Shoulders) over a period of several years from 1976 to 1999, with a minimum follow-up period of four years. Radiopharmaceutical used were as follows: Gold Colloid (Au-198): 58 joints, Rhenium-186: 20 joints; Y-90: 26 joints. Follow-up evaluation revealed no haemarthrosis in 70% and reduced haemarthrosis in 21%, while in 6 joints there were no response (failure). Overall good results were obtained in 91%. With regard to chromosomal abnormalities, the study did not reveal any longstanding pre-malignant chromosomal abnormalities.

Autonomously functioning toxic adenomas are a common cause of hyperthyroidism. Surgery, radioiodine and percutaneous ethanol injection into the nodule are effective therapies. Radioiodine therapy is increasingly used as first line therapy especially in elderly patients. Radioactive iodine I-131 seems to be a good therapeutic option with low incidence of post-therapy hypothyroidism. The important therapeutic effect has also been the regression in nodule size. The aim of this study was to investigate the effect of radioiodine therapy on the size of toxic adenomas.Forty-six patients with age range of 37-76 years (Mean age=60.9 years) were followed up for a period of 12 months after I-131 therapy for toxic adenomas. Thyroid hormone levels (T3, T4 and TSH) were determined. Each patient was subjected to ultrasound and radionuclide scanning of thyroid gland at 3,6 and 12 months following I-131 therapy. Successful treatment was defined as control of hyperthyroidism and reappearance of extra-glandular thyroid tissue on Thyroid scan, which were suppressed by the hyperactive nodule prior to therapy. The volumes of the thyroid pre and post-therapy were estimated by US using the formula of ellipsoid model (ð/6 x length x width x depth). The therapeutic

122-VENHow safe is radioactive Synoviothesis? Fernando-Palazzi F, Viso R, Chakal F. Orthopaedic Unit. National Haemophilia Center. Caracas. Venezuela

123-BOHEffect of radioiodine therapy on thyroid nodule size in patients with toxic adenomasRajkovaca Z, Mijatovic J, Skrobis M, Kovacevic PDepartment of Nuclear Medicine, Clinical Centre Banja Luka & Department of Physiology, Medical Faculty Banja Luka, Bosnia & Herzegovina

S-65



dose of I-131 was calculated for each patient by the following formula: 12 mCi x 100/24 hrs RAIU. Patients received a single dose of I-131 and the range of administered I-131 dose was 825 1221 MBq. Results revealed that 42 patients (91%) became euthyroid in three months after I-131. All patients became euthyroid in 6 months. The adenomas were reduced in size from a mean of 18.23+11.21 ml to 7.38+3.48 ml during the 12 months follow up. This was highly significant (p<0.05, t=3.408). The extra-nodular thyroid volume did not change following therapy (12.2+7.4 ml pre-therapy vs. 11.8+7.1 ml post therapy at 12 months).The results of our study showed that I-131 can successfully treat not only the functional state of thyroid adenomas, but it can also reduce the volume of the nodules effectively.

Author

Abdelrazek SAbtroun SAfanasieva NIAfroz S Ajdinovic B Alam F Aleknavicius E Ali N Ali S Allen BJ Al-Nahhas A Alonso O Amaral H Anand YNI Ang S Ansari S Anselmi OE Aouli S Archimandritis SCArtiko V Asghar S Ashok P Astapieva OM Azra P Bal CS Bandopadhyaya GP Baranauskas Z Barrenechea EABasak B Baum RP Bayarmaa B Beatovic S Begum F Begum R Beibutov Sh.M Beiki D Benlabgaa R Bernal P Berzina A Berzina DBesic N Birkenfeld B Botev V Bouyoucef SE Bouziotis P Brecelj J Brill AB Budlewski T Burneckis A Buscombe JR Cano RA Castro M Caviglia H Chae I-H Chakal F Chandrashekar N Chatal JF

Page No.

4712

57,5813521541141456

46,55591832

19,4716,37

1812295043345843

31,343241

19,44,45,46,4733

25,274251161713

7,3812193939

53,5447,48

18122953604741

19,40,5543,44

431259653129

Author

Chau T Chen S Chinol M Chinwan BP Choudhury PS Chua M Chung JK Codorean I Coudeu I Cutler CS Dang Y Das BK Davidovic B De la Fuente H De Los Santos JO Dewan AK Dey NR Divgi C Dondi M Dougall P Dudov A Duldulao MA Dumitriu L Eftekhari M Ellmann A Engelbrecht HP Enkhtuya B 41Erdenechimeg S Esfahani AF Fallahi B Fard-Esfahani A Farhad Ghadiri MD Fawzy A Fernando-Palazzi F Fettich J Freundschuh MP Galatros G Gaston JC Ghafoorian H Ghahremani AR Gherghe M Ghita ST Giannone C Gil C Goh A Goldenberg DM Goldstein A Gonchigsuren D Griesinger F Grmek M Grushka GV Gutierrez C 5Haddad PHadjieva T Han R Hanzal A Haque FS

Page No.

1919183435455950186320

36,415018223533

19,41,6419,59

34184649

37,3838,50

63

19,41,4237373838226553291246383849501218522949412953589

3818511217

Author

Harousseau JL Henni-Haddam F Hilson AJW Hoefnagel CA Hofmann A Horak ID Hossain R Hossain S Huglo D Hussain R Islam N Islam SKM Izadian ES Jaksic E Jankovic Z Jaukovic L Jehan AH Jehangir M Jeong JM John P Jordanou JJoshi ND Julka PK Kabir MF Kakhki VRD Kaliska L Karim MA Kasparek R Ketring AR Khan B Khodjibekova MKirsch CM Kleinman S Kling A Knapp FF Knut Liepe Kociura-Sawicka A Koeckeritz UKonior MKontogeorgakos D Korol P Korsak A Kostic K Koumarianou E Kovacevic P Krishna BA Krishnakumar R Kropp J Kulakiene I Kumar A Kumar R Kuprionis G Lateiner J Laureta EG Lee MC Lewis MR Li J

Page No.

29124042132917

14,172916141437515252174319133034

31,34157

5215,16,17

21633464291848

19,59,6024,26

47

483057485029653336

27,29,5940

19,3431,32

402946396319

Author Index


S-66


Author

Limouris G Lyra M Majlis A 18Malhotra A Malhotra G Mansouri B Marinescu G Markovic S Martinez F Maulik SK Mazilu C Meigooni AS Meller J Mendoza G Miah SH Mijatovic J Mikalauskas V Mikolajczak R Mirzadeh S Mishra SK Missailidis S Mititelu MR Mitsokapas NMohanty BN Momta S Morales B Morales R Morschhauser F Mushtaq AMuthu GS Muzhychuk OV Nair O Nanayakkara D Nasirova FJ Naumann R Navarra S Nazarenko S Neves M Nicolini JO Nisa L Obaldo J Obradovic V Ogbac R Oliveira A Ong A Onkhuudai P Onsel C Otakar Kraft Padhy AK Paganelli G Pandey D Pant GS Papanikolos G Parfienczyk APaul AK Pawlak DPeix A

Page No.

29,3029,30

31,32,34,36,41411

50514432503829

43,44156540486036555029361718

43,4429

3258345413 2945234812

16,1746504748

44,4519,41

5920,21

19,41,46,59183434

29,30

15,164859

Author

Perkins A Petrovic N Phinou P Plonska E Poksi A Postigo JPourbeigi H Pradhan PK Pruzzo R Pucar D Pusuwan P Quilieva AO Rahman HA Rahman MS Rahman MU Rahman SH Rajini TR Rajkovaca Z

Rashid HRasulova N Rath GKRay S Reyes C Reynen KReznak I Rimbu A Rogowski FRojas A Rossi R Roznere L Saavedra P Saesow N Saghari M Salas A

SamarinaG San Luis TOL Sanchez PSankar R Santiago J 45Sarika SasakiY Saw MM Schaffarich MP Schwarzbartl-Pevec A Seam RK Sellah M Seminario C Senftleben S Senthamizhchelvan S Senthilnathan MS Sergieva S Shahidullah M Sharma SK Shiraliyev OK Shukla J Sinzinger H Skrobis M

Page No.

55,56502959234438

36,4118521913

15,161 6

171632651464343318

215047181839445537442347

32

34385213

53,54351

4327344118143313321365

Author

Snehlata Sohaib M Solav S Soldner J Sood A Sopotyk ASoroa V Srivastava D Srivastava SC Stabin M Staudenherz A Storto G Strauß H-J Sundram FX Szilvasi I Szumowski PTaghizadeh-asl M Takavar A Tanada S Tiskevicius S Torres F Tripathi M Tsevelmaa L Turner JH Vajauskas D Varas M Varma IK Varvarigou AD Vasiliev L Ya Velazquez Espeche MH Vereb M Vevere I Vidergar-Kralj B Vilchez C Vinjamuri S Viso R Vlahos L Vlajkovic M Vogel C Warbey VS Watanabe N Wegener WA Wehrmann C Wiseman G Xanthopoulos SYasmin S Yousuf M Zagar I Zelek Z Zhang W Zheng R Zikos C Zuchlinska M

Page No.

36433025354712196260135925

19,41,5259473838384144

31,364212401832295712523954

57653050184038292764291743

53,544819192948

Author Index

S-67

10th COLOMBIAN CONGRESS OF NUCLEAR MEDICINE

Third Announcement:

You are most welcome to participate in the 10th Colombian Congress of Nuclear Medicine, scheduled to be held at Bucaramanga, Colombia, from November 4 to 6, 2005. Bucaramanga is a beautiful city close to Bogotá (30 minutes by plane), located at 1000 meters above sea level. The venue of the congress will be ¨Palonegro¨, South of the city, 15 minutes by road from downtown and 30 minutes from the airport. It is a paradise resort with several sporting facilities: golf field, swimming pools, tennis and a hotel with comfortable rooms and

auditoria where all the lectures, scientific sessions and business meetings will be held. The main economic activity of the area is trading in footwear and garments. Their gastronomy is recognized by the delicious variety of meat and the typical corn bread called: ̈ arepa¨.

For further information please contact:Dr. Leonardo Cadavid: [email protected] ,President.Dr. Patricia Bernal: [email protected], scientific committee


World Journal of Nuclear Medicine, Volume 4, Number 3, July 2005

AOTA Meeting in Philippines

FIRST ANNOUNCEMENT:

8th Asia Oceania ThyroidAssociation Congress

February 4-6, 2007

ASIA & OCEANIA THYROIDASSOCIATION

D AI SO SR OY CH IT A

TE

IN OI

NPP ,I INLI CH .P

1964

Organizing Committee:Advisor:

Dr Teofilo San LuisChairman:Dr. L. Mercado-AsisChairman, Scientific Committee:Dr. E. Barrenechea

Secretariat:

St Lukes Medical Center10th Floor, Room No. 1002

South Tower Cathedral Heights BldgE. Rodriguez Sr Avenue

Quezon City 1102Tele-fax: 00-63-2-7252133, 7230101,

9252891Attention: Dr. E. Barrenechea

[email protected]

Venue:

Westin PhilippinePlaza Hotel, Manila

LATIN AMERICANTHYROID SOCIETY

ETA

AssociationEuropean Thyroid

A M E R I C A N

T H Y R O I D

A S S O C I A T I O N

F O U N D E D 1 9 2 3