Department of Nuclear Medicine

Annual Report Nuclear Medicine & PET Research 2004-2005 1

Department of Nuclear Medicine & PET Research

Annual Report 2004-2005


Contents

I. Introduction 3

II. Mission 4

III. Organisational structure 7

IV. Expertise and facilities 10

V. Patient care 13

VI. Education and professional training 17

VII. Research and development 19

VIII. Societal impact 25

IX. Current trends and perspectives 28

X. Personnel 30

XI. References 35


I. Introduction In 1997 the VU University Medical Centre (VUmc) initiated an interdepartmental PET project (PET centre), following preparatory activities of the Department of Nuclear Medicine. The mission of this PET centre was to combine methodological and clinical PET research with diagnostic applications, the latter being focussed on the development of diagnostic guidelines. Studies were performed in collaboration with the RadioNuclide Centre (RNC) of the VU University (VU), active in radiochemistry research since 1975, and with the BV Cyclotron VU, responsible for the production of the required radionuclides. Moreover, at the same time, the RNC was equipped with an experimental PET scanner and GMP compliant radiochemistry laboratories. To guarantee a coherent approach with respect to the various PET activities, the board of directors of VUmc and VU decided to combine all activities into a single department. Consequently, on January 1st, 2004, the VUmc Department of Nuclear Medicine & PET Research was formed, incorporating the former Department of Nuclear Medicine, the PET project and the RNC. Setting up the organisational structure of this new department took place in 2004 and was finalised in 2005. The present report is the first annual report of the new department, covering the years 2004 and 2005.


II. Mission The integration of nuclear medicine facilities and expertise at the VU-campus allows for operationalisation of this mission into a comprehensive spectrum of activities covering patient care, education and training, and research.

i. Research The aim of the Department of Nuclear Medicine & PET Research to be an expert centre for the development and application of PET, is in line with the ambition of the VUmc to be a knowledge centre for health care. PET was developed in the nineteenseventies as a non-invasive in vivo research technique for pathophysiological investigations, which provided the possibility to obtain new information on human disease. Over the last 10 to 15 years, it has been “discovered” as a sensitive diagnostic technique, especially for detecting metastases in oncology, resulting in PET being the fastest growing technique within the domain of medical technology todate. As a quantitative molecular imaging technique, its potential for assessing effectiveness and action of therapy has also been recognised. Several pharmaceutical companies have invested in their own PET facilities or entered into a structural collaboration with a PET research centre in order to evaluate new drugs in vivo. Given this potential, it will only be a matter of time before PET will be used for individualised therapy.

The mission of the department is to develop, validate and implement radiopharmaceutical (‘molecular’) technology for diagnosis and treatment of disease.


Based on the considerations given above, the Department of Nuclear Medicine & PET Research has decided to focus its research on PET, as is highlighted in the name of the department. As such, the activities of the department cover the entire process from biological hypotheses to implementation of technologies into clinical practice, with the inherent ability to add to the knowledge (both from conceptual and practical points of view) of diseases and their treatment. The multidisciplinary expertise, brought together within the new department, and the investments in infrastructure not only provide the means, but also create the moral obligation to aim for a leading position in the world, in particular with respect to scientific PET research. The department aims to achieve this goal within the next five years by continuously investing in talented scientists, radiochemical research, modelling research and medical technology assessment. ii. Patient care The aim of the Department of Nuclear Medicine & PET Research is to provide state of the art diagnostic and therapeutic nuclear medicine for the VUmc and as a referral centre for hospitals without access to nuclear medicine facilities. Moreover, the present infrastructure finally allows for newly developed technology to be clinically validated and implemented from within the department, before dissemination into general practice, ie. to carry the technology from bench to bedside.


iii. Education and training As an expert centre, it is the intention of the Department of Nuclear Medicine & PET Research to take a leading role in the multidisciplinary education and training of professionals, working in the field of nuclear medicine & PET research, as well as of those who are using this technology for patient management. It is felt that this part of the mission directly follows from the departments’s research activities and expertise in patient care. Standardisation and harmonisation (from acquisition to interpretation) are the main challenges for new technologies in clinical practice. To achieve the aims mentioned above, the Department of Nuclear Medicine & PET Research considers collaboration to be a key principle. The department continuously seeks collaboration with research groups both within and outside the VUmc.


III. Organisational structure On January 1st, 2004, the newly formed Department of Nuclear Medicine & PET Research comprised a staff of 76, originating from the former department of nuclear medicine, the RNC and the PET project. The rationale behind this integration was to concentrate all expertise related to the development and application of radionuclide tracers into one organisational unit in order to guarantee a coherent an efficient approach to these activities. Integration of the three parties mentioned above required an extensive reorganisation, especially as it involved a change of employer (from VU to VUmc) for employees of the RNC. This reorganisation was established following extensive consultation of all employees and according to legal requirements for such a reorganisation. Many members of the new department made a considerable effort into the process of reorganisation. Apart from the formal requirements, it was recognised that a concerted approach was necessary to obtain a truly coherent department. Following a general kick-off meeting in June 2004, several multidisciplinary working parties were formed. These working groups formulated, discussed and, where necessary, proposed alternatives for the previously determined essential processes within the department. Merging preclinical and clinical fields and workers implied more than just a logistic manoeuvre. It also required an adaptation to a different culture. Despite several complicating factors (prof. Teule leaving for University Hospital Maastricht, followed by an open procedure for his succession; unsuccessful procedure to find a suitable professor of radiofarmacochemistry and head of the chemistry section), the formal process was completed in the fall of 2005. The new Department of Nuclear Medicine & PET Research is divided in (professional) sections, led by section heads. In addition, within each section, one or more coordinators have been appointed, who are responsible for organising certain areas of work. Operational activities, such as personnel, administration, finances and secretarial assistance, are embedded in a dedicated operational office. Finally, there are two heads of department. A diagram of the organisational structure of the Department of Nuclear Medicine & PET Research is given below. This diagram also highlights that many activities are incorporated into projects, both scientific and non-scientific. Given the size of the new department and the very strong research component, it was decided to appoint two heads of department, one responsible for patient care and professional training (prof. G.J.J. Teule), the other for research and education (prof. A.A. Lammertsma). On September 1st, 2004, prof. Teule took up a new position at the University Hospital of Maastricht and dr. O.S. Hoekstra was appointed as acting head of department (patient care and professional training). At the same time an open procedure was initiated to fill the vacant chair. As a result of this procedure, dr. Hoekstra became full head of department for patient care and professional training, and was appointed as full professor in Nuclear Medicine in November 2005. As part of the reorganisation it was decided to create a new chair of radiopharmacochemistry, in collaboration with the Faculty of Sciences and the BV Cyclotron VU. Holder of this chair would become head of the chemistry section and, in line with the importance of radiochemistry for the department, member of the managing team (MT), together with the heads of department and the manager of Cluster I to which the department belongs. An international procedure to find a suitable candidate was started in the second half of 2004. In the summer of 2005 it became clear that no suitable candidate could be found. To guarantee continuity within the chemistry section, prof. G.A.M.S. van Dongen was appointed as acting section head (and member MT). Although his official appointment took effect on January 1st, 2006, he already was involved in a consulting role during the last months of 2005.


Finally, prof. J.E. Leysen joined the department in a consulting role from November 1st, 2004. Formerly, she fulfilled this role at the Department of Pharmacology. As this department was reorganised and prof. Leysen had a strong interest in molecular imaging, a move to the Department of Nuclear Medicine & PET Research was logical, thereby substantially strengthening pharmacological knowledge within the department.


Organisational Structure Department of Nuclear Medicine & PET Research

Operational office

Administration patients projects Secretaries Finances Personnel

PhysicsBiology Chemistry

Projects

Projectleader/ (senior)- investigator

Projectleader/ (senior)- investigator

Radiation safetyQuality GMP NIAZ Office / lab space ICT Hotel function RNL RNC P h

Pharmacist

PharmacyVUmc

Diagnostics & Therapy

Nucl MedTechnology

Head of Department Patient care Professional training

Head of Department Research Education

Instrumentation

Abbreviations used - GMP: good medical practice; NIAZ: Nederlands Instituut voor Accreditatie van Ziekenhuizen; RNL: radionuclide laboratory


IV. Expertise and facilities The Department of Nuclear Medicine & PET Research of the VU University Medical Centre (VUmc), together with the BV Cyclotron VU, provides a means to fully develop radiopharmaceuticals for PET and SPECT in both animal and human studies. Expertise ranges from radionuclide production, through new tracer development and preclinical evaluation, to clinical use of new and existing tracers with highly qualified specialists who operate in a truly multidisciplinary environment. The whole process can be performed according to state-of-the-art GMP/GLP/GCP standards. i. Available tracers Licensed PET radiopharmaceuticals 11C labelled: flumazenil, PK11195, raclopride, verapamil, R116301, palmitate, R107474,

DASB, PIB. 18F labelled: FDG, FLT, fluoride, FP-β-CIT, MPPF, FDDNP, proline. 15O labelled: H2O, O2,, CO, CO2. In development 11C labelled: docetaxel, WAY100635, deprenyl, methionine. 13N labelled: N2. 18F labelled: FAZA, fluoromethylcholine. Licensed SPECT radiopharmaceuticals

123I labelled: R91150, iomazenil, hippuran, iodine, MIBG, β-CIT. 81mKr: Generator. Monoclonal antibodies and peptides Validated and universal procedures are in place for labeling antibodies and peptides for pharmacokinetics/biodistribution studies (99mTc, 186Re, 123I, 125I, 131I, 111In, 177Lu), SPECT imaging (99mTc, 186Re, 123I, 131I, 111In, 177Lu), PET imaging (68Ga, 89Zr, 124I) and radioimmunotherapy (186Re, 131I, 177Lu, 90Y). In recent years more than 15 different radioimmunoconjugates have been produced for clinical evaluation, either in house or at other institutes. Several R&D collaborations with biotech companies are ongoing. All quality tests are in place: radiochemical purity, conjugate stability, substitution ratio, antibody integrity, immunoreactivity, preclinical in vivo behavior, sterility, pyrogenicity and immunogenicity. ii. Available analytical methods General models and data analysis tools Single tissue, two tissue (reversible and irreversible), reference tissue (Lammertsma), steady state (Jones, Lammertsma) and linearised (Patlak, Logan, Blomqvist, Ichise) models, spectral (Cunningham), cluster (Ashburner) and factor (Hermansen) analysis, basis pursuit (Gunn), parametric imaging (linearisations, basis functions), metabolite models, dose ranging studies, biological half-life studies. Tracer kinetic models for specific applications Perfusion, perfusable tissue index, glucose metabolism, oxygen utilisation, fatty acid metabolism, blood volume, haematocrit, integrity blood-brain barrier, P-glycoprotein function, pH, osteoblast activity, TK1 activity, MAO-B activity, dopamine D2 and D1 receptors, dopamine transporters,


central (GABAA) and peripheral benzodiazepine receptors, serotonin 5-HT1A receptors, NK1 receptors. iii. Available biological methods Methodologies Several in vitro, in vivo and ex vivo techniques such as autoradiography, binding studies, cell cultures, molecular biology techniques, FACScan analysis, enzyme assays, (pretreated) biodistribution studies, animal PET, anesthaesia (both inhalation and injection). Animal species Rats, mice, rabbits, minipigs, rhesus monkeys, transgenic mice, nude mice and rats. Animal models Oncology: breast, cervical, head & neck, lung, prostate and colon cancer, glioma. Neurology: Parkinson’s disease, depression, neurotrauma, MS, epilepsy. Cardiology: minipigs. Other: osteomyelitis. iv. Clinical research studies General

Medical technology assessment (MTA), PET in drug development. Neurology

Alzheimer’s and Parkinson’s disease, epilepsy. Psychiatry

Anxiety & depression, schizophrenia, post traumatic stress disorder. Cardiology

Myocardial ischemia, heart failure. Oncology (only main studies)

Lung, breast and head & neck cancer, response monitoring (chemo- & radiotherapy). v. Facilities State-of-the-art whole body PET camera (HR+, CTI/Siemens); High resolution research PET camera (HRRT, CTI/Siemens); 3 gamma cameras (2 dual-head systems, Siemens); 3 therapy rooms (located within the ward of the department of haematology); Several gamma probes (including a laparoscopic probe); Medrad infusion system (controlled injections/infusions); Veenstra on-line blood withdrawal & detection systems; Beta-probe; RDS111 cyclotron (CTI); Oxygen-15 gas delivery system; 25 Separate type II labs for working with radioactive material; GMP compliant hotlab with 6 hotcells; 3 research hotcells, 1 shielded fumehood; Metabolite analysis lab;


Small animal housing facilities; Multiple HPLC and GC systems; Multiple gammacounters and betacounters; Phosphor imager. In addition, radioactivity is produced by BV Cyclotron VU (general manager Dr. P.J. van der Jagt), where the following facilities are available:

Philips AVF 30 cyclotron; 2 IBA 18/9 cyclotrons; Commercial production of [18F]FDG, and 81mKr and 123I labelled products.


V. Patient care It will be clear that, with respect to patient care, there are relationships with most departments of VUmc. Traditionally, there have been strong collaborations with the departments of internal medicine (in particular endocrinology, pulmonology, haematology and medical oncology), cardiology, surgery, otolaryngology, neurology, orthopedics, pediatrics, and more recently with the department of clinical epidemiology & biostatistics as a result of the PET technology assessment efforts. Since the introduction of PET in 1997, the required co-reading with radiological tomographic imaging (CT, MRI) has induced a tight interaction between dedicated radiologists of the VUmc and nuclear medicine physicians. The existing collaboration with the department of radiology will intensify after the installation of the planned PET-CT scanner in 2006. The same will be true for the collaboration with radiotherapy, as this scanner will partly be used for treatment planning. In oncology, the geographic target area is the the region administered by the Comprehensive Cancer Centre Amsterdam (IKA). In neurology, the department plays a national role for diagnostics in the presurgical work-up of patients with medically refractary epilepsy. After transferring the at the time substantial number of bone density measurements (DEXA) to the department of radiology (2001), the range of activities has been dynamic, primarily due to developments related to PET. The total number of activities, however, is rather stable at 8000 per year, with an obvious trend towards more complex procedures, especially in the PET domain. The main activities are listed in the table below.

2004 2005 cardiology 2212 (7%*) 2345 (9%) endocrinology 818 (4%) 722 (4%) inflammation 74 (70%) 94 (88%) nephrology 334 (0%) 358 (0%) neurology 185 (74%) 217 (63%) oncology 1355 (60%) 1447 (60%) pulmonology 1619 (37%) 1392 (52%) skeletal 963 (0%) 1074 (0%) miscellaneous diagnostic 39 (0%) 71 (0%) therapy 243 210

* percentage PET procedures

The relative contribution of PET procedures to the total number of nuclear medicine investigations has increased steadily over time, in line with international trends. Without new facilities, no further increase would be possible, since the scanner capacity is fully exploited. The vast majority of PET scans was for oncological purposes, with 50% being performed for hospitals other than the VUmc. The main indications were lung cancer, malignant lymphoma and colorectal cancer. To promote effective use of the nationwide limited capacity, a policy was adopted in which clinicians were obliged to consult attending nuclear medicine physicians before referring patients for PET. The only exceptions were scans for indications that already had been incorporated into guidelines. For these ‘guideline-scans’ dedicated slots were reserved to limit waiting lists. From


time to time, the scanner had to be restricted for referring physicians within the IKA region to avoid unacceptable waiting lists for patients in the VUmc’s geographical area. In 2005, however, it was necessary to work in shifts in order to cope with the increasing number of valid requests. Finally, to optimise the use of PET in general, the department actively contributed to all national multicentre studies evaluating the cost-effectiveness of FDG PET in oncology. Several years ago, the department chose to focus on PET and to deliberately refrain from several nuclear medicine activities, such as 131I-MIBG therapy and 123I DAT SPECT. In order to concentrate expertise, those patients were referred to neighbouring centres. The department actively contributed to multicentre studies (ANTELOPE projects) investigating the role of CT angiography for diagnosis of pulmonary embolism. This development has contributed to the relative increase of PET within the pulmonology domain. In addition, inflammatory processes were increasingly diagnosed and monitored using FDG PET rather than 99mTc, 111In and 67Ga labelled compounds. In cardiology, SPECT studies (diagnosis of ischaemia and assessment of viability) comprised 90% of the non-PET procedures. Finally, dissemination of 131I therapy facilities tended to increase the relative proportion of high dose therapies for patients with thyroid cancer. In 2006, a national guideline on thyroid cancer is expected, which should address the appropriate balance between diffusion of this technology and the need to maintain expertise within a multidisciplinary setting. i. Incidents related to patient care In 2004 and 2005, six incidents were reported, three in each year. Five were related to lack of compliance with internal rules and regulations, four of which occurred in the setting of routine patient care and one in the research area.

June 2004: Incorrect radiopharmacon prepared for cardiology stress test study; discovered prior to injection; examination rescheduled. Background: deliberate deviation from routine procedure ordered by nuclear medicine physician (Tl-201 rather than Tc-99m-Myoview) not recognized by administrative section. Action: signaling system for specific protocol deviations. October 2004: Examination filed incorrectly by technologist (wrong patient name); discovered by head of technology section and corrected prior to archiving. Background: human error in combination with lack of automated check procedure. Action: manufacturer software contacted, but no solution provided; in-house developed software procedure installed. January 2005: During five subsequent stress tests, administered adenosine dosage too low; patients rescheduled. Background: series of errors: department of pharmacy incorrectly delivered 40 microgram/l dosages rather than 6 mg/ml; technologist and attending physician failed to check dosage. Action: pharmacy checks dosages prior to delivery; double check by technologist / physician prior to any injection; drug label adhered to medical record. April 2005: Incorrect radiopharmaceutical administered (18FDG rather than 11C-tracer). Background: protocol violation (see above), partly induced by time pressure at PET. Action: repeated instruction (see January 2005). November 2005:


Patient complaining of partial hypesthesia at first digit after arterial cannulation for research PET study. Background: retrospective complaint; no irregularities during PET examination. Action: referral to vascular surgeon: no objective abnormalities; expectative policy.

The remaining incident was a complaint concerning extensive delay of transportation back to the referring hospital due to failing ambulance logistics. ii. Radiation safety Administration of radiation safety, as required by Dutch law (Kernenergiewet), can be found in the annual reports by the “dienst Veiligheid & Milieu”. These reports can be found at the VU intranet site https://www.intranet.vu.nl/Arbo_en_Milieu/index.cfm. iii. Patient satisfaction survey The department presented and internally discussed the results of an internally designed and managed survey on patient satisfaction early 2004. The survey pertained to the 2nd half of 2003 and was in fact a follow-up to a similar procedure in 1998. Within a time frame of two months, a questionnaire with 20 multiple-choice questions was mailed to 286 patients, a few days after they had undergone a diagnostic or therapeutic procedure in the department. The survey comprised a mix of in-patients and out-patients, who had been referred for conventional nuclear medicine procedures or PET, both from within the VUmc and from other hospitals, and who represented a range of age categories. At the time of the patient’s visit, employees of the department were unaware whether the patient would be approached, but they were aware that the survey was running. The complete (Dutch) version is available from the secretariat of the department. The survey pertained to items on waiting lists (actual and subjective perception), flexibility of the department to adapt scheduling of the procedures to the patient’s preferences, quality and actual delivery of pre-test information (verbal, leaflets), logistic procedures at the time of scanning (delays, communication), attitude of personnel, quality (spatial, privacy) and hygienic state of waiting and scanning rooms, and finally a subjective assessment of the full procedure. The response rate was 57% (compared to 50% in 1998). The findings are summarized in the following table. a. Average results of answers to the summarising question ‘how would you rate this department on….’ on a scale of 1-10 (1: extremely poor … 10: excellent); NM = nuclear medicine. NM 1998 NM 2003 PET 1998 PET 2003 Pre-test information 8.1 7.6 7.8 8.1 Attitude of staff 8.5 8.4 8.4 8.6 Attention for privacy 8.4 8.2 8.1 8.4 Facilities 7.7 7.6 7.4 7.9 General impression 8.1 8.0 8.2 8.2


b. Relative proportion (%) of ratings below ‘7’ NM 1998 NM 2003 PET 1998 PET 2003 Pre-test information 10.5 16.8 15.8 7.7 Attitude of staff 3.8 4.0 5.3 1.9 Attention for privacy 4.1 5.4 0.0 4.1 Facilities 18.4 17.2 26.3 11.5 General impression 5.9 3.3 10.0 6.1 Even though it was felt that results in 1998 had been encouraging, a few issues needed improvement: there were apparent deficiencies in the patient information process, especially for PET (at the time, PET had been operational for just one year). More specifically, available patient information leaflets were not adequately distributed when scans were ordered. Interestingly, patients reported that employees of the department compensated for this lack of written material by providing adequate information at the time of the procedure. Nevertheless, efforts were undertaken to improve the quality and availability of written material. Moreover, for PET, the survey had not distinguished between patients referred for diagnostic and research procedures. Therefore a more detailed survey on the quality of information for PET procedures was performed (conducted by A. Giacomo-Russo, supervised by prof E. van Leeuwen). Based on the outcome of this survey, procedures were adapted, apparently with success. Finally, criticism was most prominent with respect to the lack of adequate facilities within the department. This is a longstanding problem (not uncommon in VUmc), which indeed urgently requires improvement.


VI. Education and professional training i. Undergraduate and graduate education In 2005, the VUmc rigorously changed the format of its basic medical training curriculum (see http://www.vumc.nl/hoofdframes/onderwijs/index.html). Since then, the Department of Nuclear Medicine & PET research provides tutors for training of first-year students (in 2005/2006: drs A.A. Geldof and E.F.I. Comans). In the ‘old’ curriculum, the department provided several lectures in the initial three years of medical training, took part in or organised several practical courses, organised on-site courses for medical interns and provided supervised training for individual students. Several members of staff contributed to courses organised by the VUmc research institutes, to their master student programs and/or supervised training for individual students. Via the Department of Clinical Epidemiology and Biostatistics, Hoekstra provided several practical courses to undergraduate students regarding critical appraisal of literature on diagnostic tests. Apart from involvement in education of medical students, members of staff also contributed by giving lectures at undergraduate courses of the Faculty of Sciences (Medical Natural Sciences track) and the Faculty of Psychology and Education (Neuropsychology track) of the VU. In addition lectures were given for the Technical University of Delft (Medical Physics programme). In addition to lectures the department received students for extended periods of time (3 to 9 months) of supervised scientific training from the Faculty of Sciences (Medical Natural Sciences track) and the Faculty of Earth and Life Sciences (Medical Natural Sciences track) of the VU. Finally, lectures were given at several local and national graduate courses. ii. Postgraduate education in PET With the advent of PET in clinical practice, standardisation again is a major topic in nuclear medicine. Furthermore, to keep pace with the rapid diffusion of PET in Dutch clinical practice, skills need to be disseminated and implemented. This applies to pre- and postgraduate settings with regard to both diagnostic (nuclear medicine physicians, radiologists) and referring specialists. Based on the remit of academic medicine, the department has taken the lead in developing educational activities in relation to PET, at the level of both medicine and physics. In 2000, when carrying out the top-down national research health care programme on PET, a lack of appropriate postgraduate learning facilities for PET were recognized. In addition, experience at the EANM (European Association of Nuclear Medicine) teaching facility in Vienna (Comans) suggested that a more intensive and active programme was required. In an attempt to further professionalise this training, Comans became a member of the NVMO (Dutch Society for Medical Education) and took courses in didactics. Since then, the Department of Nuclear Medicine & PET Research has organised several cycles of courses on oncological PET in a skills lab format. For this purpose, an extensive structured PET database was set up, and there was active and enthousiastic expertise input from the VUmc departments of pulmonology (dr. E.F. Smit), surgery (dr. M.A. Paul), otolaryngology (dr. R. de Bree), haematology (dr. J. Zijlstra-Baalbergen) and clinical epidemiology & biostatistics (prof. dr. M. Boers). Teaching files were prepared with the help of several medical and PhD students. Course participants came from community hospitals in the Netherlands, both within and beyond the catchment area of the Comprehensive Cancer Centre Amsterdam (IKA). Especially the link with the Comprehensive Cancer Centre South (IKZ, Eindhoven) became tight, resulting in IKZ inviting one of the NGP staff members (Hoekstra) to become one of their two PET consultants.


Finally, since 2004, NGP provides the in-house PET training of the nuclear medicine residents of the University Medical Centre Leiden, which at present does not have its own PET facility. Recognizing that education of referring clinicians might be an important tool to promote effective use of PET, the department became involved in pre- and postgraduate courses for surgeons, radiologists, pulmonologists and medical oncologists. In addition, members of the department often (about 20 times) were invited by medical staff of community or university hospitals, by their board of directors, or by tumour working groups of comprehensive cancer centres to give lectures and/or discuss the details of PET in clinical practice. Moreover, it was recognized that educating the principles of nuclear medicine to those working in preclinical science was equally important to stimulate the field. Therefore, lectures were also given at the annual courses of the NVVO (Dutch Society of Oncology). Finally, Lammertsma was involved in the organisation of the (on average biannual) international PET Pharmacokinetic Course, in which the first principles of tracer kinetic modelling, a prerequisite for quantitative PET studies, are taught. iii. Professional training As member of the board of the Dutch Society of Nuclear Medicine (NVNG), Comans had taken the initiative to modernise the training of nuclear medicine residents in 2001. From 2004, he actively participated in the working party on restructuring nuclear medicine training of residents (WEMONG). Pijpers chaired the NVNG’s educational committee, which organised the annual courses for nuclear medicine residents, and all members of staff (physicians as well as physicists) actively contributed to these courses. Finally, Lammertsma was chairman of the Executive Committee for Board Registration of the Dutch Society of Clinical Physics and, as such, responsible for the quality of training of clinical physicists in the Netherlands. Over 2004 and 2005, the Department of Nuclear Medicine & PET Research was responsible for, on average, the training of five residents in nuclear medicine (responsible physicians: prof. G.J.J. Teule/dr. J.C. Roos until Sept 1st, 2004; dr. R. Pijpers/dr. O.S. Hoekstra thereafter). A total of five completed their training within this period, and several of them took additional PET courses during fellowships at the department. In addition, the department was responsible for, on average, the training of four residents in clinical physics (responsible physicist: dr. A. van Lingen), with one completing his training within this period. Moreover, ten nuclear medicine technologists followed their in-service training in the department (responsible technologist: C.S.M. de Jong-Greuter), with all but one finishing their training within the reporting period. Finally, three pharmacists performed a research project within the department as part of their professional training. iv. Education in radiation safety

Both in 2004 and 2005 the department organised (coordinator: dr. G.W.M. Visser) 5 courses “Working with radioactivity”. This course is compulsory for VU and VUmc personnel, who need to handle radioactivity as part of their job. The course is at such a level that participants are sufficiently equipped to take the (state) examination radiation safety level 5B. In addition, members of the department lecture at incidental radiation safety courses organised by the radiation safety group of the VU. Finally, members of the department provide radiation safety seminars and instructions for trainees and students, whose stay at the department is too short to be able to follow the more formal course mentioned above.


VII. Research Nearly all research of the Department of Nuclear Medicine & PET Research is embedded within four VUmc based research institutes (V-ICI, ICEN, IcaR-VU, MOVE) and one VU/UL research institute (LACDR), the latter primarily covering radiochemistry research.

V-ICI: VUmc Institute for Cancer and Immunology ICEN: Institute for Clinical and Experimental Neuroscience ICaR-VU: Institute for Cardiovascular Research MOVE: Institute for human movement research LACDR: Leiden/Amsterdam Centre for Drug Research

The only exceptions are a number of research projects, which are carried out in collaboration with groups outside the VUmc. Most scientific research is carried out in collaboration with other groups, both from within and outside VUmc. This is best illustrated by the large number of PhD students from various departments, who perform their research within the Department of Nuclear Medicine & PET Research. The (former) department of nuclear medicine had a tradition of research related to the sentinel node procedure and, in collaboration with the department of cardiology, myocardial viability. After the introduction of PET at the VUmc in 1997, research progressively shifted towards PET. Initially, focus was on MTA studies of clinical applications of FDG PET in oncology. In addition, research concentrated on the development of quantitative procedures for routine clinical use. These procedures are now used in prospective patient studies. The steady increase of neuroreceptor ligands, together with the presence of an experimental high resolution scanner (HRRT), have led to a more prominent role of the neurosciences. This is in line with the wish of both VUmc and VU to excel in brain imaging. In addition, existing expertise in the areas of radiochemistry and modelling (development of new tracers and tracer kinetic procedures) has resulted in a research line investigating the use of PET in drug development. After the formal integration of the three entities (nuclear medicine, PET project, RNC), a formal project administration system was set up to better coordinate and streamline the various research activities. i. PhD students During 2004 and 2005 a total of nearly 50 PhD students performed research at the Department of Nuclear Medicine & PET Research, with the vast majority performing research in PET. More than half of these students performed their entire PhD research within the department. For the remainder PET constituted part of their PhD studies. Four PhD candidates defended their thesis successfully in 2004 or 2005. Most of the (applied) PhD projects were performed in collaboration with other departments. A complete list of PhD students is given under Personnel, where also involvement of other departments or institutes is indicated.


ii. Grants Ongoing january 1st, 2004 1. FDG PET top-down program ZON-MW:

a. Positron emission tomography for the prediction of long-term treatment outcome in newly diagnosed aggressive Non-Hodgkin’s lymphoma (PALET); prospective multicentre observational study; funded by ZON-MW grant no. 945-11-003 (VUmc investigators: J Zijlstra, EFI Comans, OS Hoekstra, depts of nuclear medicine & PET research and haematology).

b. PET and colorectal liver metastases (POLEM); multicentre randomized trial; funded by ZON-MW grant no. 945-11-017 (VUmc investigators: EFI Comans, J van der Sijp; depts of nuclear medicine & PET research and surgical oncology).

c. Improving and simplifying diagnostic evaluation of esophageal cancer with a combination EUS-FNA and PET (DIVAPEC); prospective multicentre observational study; funded by ZON-MW grant no. 945-11-002 (VUmc investigators: EFI Comans, OS Hoekstra, dept of nuclear medicine & PET research).

d. Screening for distant metastases and second primary tumours with FDG-PET (SCHOOL). prospective multicentre observational study; funded by ZON-MW grant no. 945-11-014 (VUmc investigators: A Senft, R de Bree, OS Hoekstra; depts of nuclear medicine & PET research and otolaryngology).

e. PRIMUS (unknown PRIMary tumours Studied with FDG-PET); prospective multicentre observational study; funded by ZON-MW grant no. 945-11-005 (VUmc investigators: R de Bree, OS Hoekstra, depts of nuclear medicine & PET research and otolaryngology).

2. The role of excitatory amino acids in neuronal damage and outcome after traumatic brain injury: assessment in patients using microdialysis and (r)-11C PK11195 PET; grant from Hersenstichting Nederland; single centre study (H Folkersma, BNM van Berckel, W Vandertop, AA Lammertsma; depts of nuclear medicine & PET research and neurosurgery).

3. Development of the long-lived positron emitters 89Zr en 124I; grant from NWO/Stichting Technische Wetenschappen (L Perk, GAMS van Dongen, JDM Herscheid, GWM Visser; depts of nuclear medicine & PET research and otolaryngology).

4. Selective targeting of angiogenesis and of tumor stroma (STROMA); grant from EU, 6th

framework (B Tijink, GAMS van Dongen; depts of nuclear medicine & PET research and otolaryngology).

5. Experimental and clinical studies using positron emission tomography (PET) for monitoring response to chemotherapy in (locally) advanced breast cancer; grant from KWF no VU2003-2822 (WGE Direcks, CFM Molthoff, G Giaccone, AA Lammertsma; depts of nuclear medicine & PET research and medical oncology).

6. Development of PET methodology for monitoring early responses to chemotherapy in breast cancer patients; grant from The Susan G. Komen Breast Cancer Foundation US Grant #IMG0402756 (J Emmering, JJM van der Hoeven, CFM Molthoff, M Lubberink, AA Lammertsma, OS Hoekstra; depts nuclear medicine & PET research and internal medicine Amstelland Hospital).

7. PIRAMID (Pathophysiological significance of myocardial triglyceride accumulation in type 2 diabetes mellitus related heart disease: the effect of pioglitazone on myocardial metabolism and function); grant from Eli Lilly NL, single centre study (VUmc investigators: L Rijzewijk, M Diamant, AA Lammertsma, HWAM de Jong; depts of nuclear medicine & PET research, cardiology and endocrinology).

8. Mechanisms of pharmacoresistance: longitudinal Positron Emission Tomography studies in experimental models of epilepsy; grant from the NEF no 02-06 (VUmc investigator: AA Lammertsma; dept nuclear medicine & PET research; in collaboration with department of pharmacology, UL).


9. Concerted Action: Neuroreceptor changes in mild cognitive impairment; European Commission, Contract QLK6-CT-2000-00502 (VUmc investigators: A Schuitemaker, M Kropholler, M Lubberink, R Boellaard, B van Berckel, P Scheltens, AA Lammertsma; depts of nuclear medicine & PET research and neurology).

10. Potential of positron emission tomography with Zirconium-89-labeled chimeric monoclonal antibody U36 for planning of radioimmunotherapy in head and neck cancer patients; grant from KWF no 2000-2155 (GAMS van Dongen, R de Bree, AA Lammertsma; depts of nuclear medicine & PET research and otolaryngology).

Acquired in 2004-2005 1. PET of cerebral amyloid load as a potential diagnostic marker for pre-symptomatic

Alzheimer’s disease; grant from American Health Assistance Association, single centre study (N Tolboom, BNM van Berckel, Ph Scheltens; depts of nuclear medicine & PET research and neurology).

2. Imaging of amyloid in pre-symptomatic Alzheimer’s disease; grant from Internationale Stichting Alzheimer Onderzoek, single centre study (N Tolboom, BNM van Berckel, Ph Scheltens; depts of nuclear medicine & PET research and neurology).

3. From hypothesis towards data-driven analysis of neuroreceptor studies with positron emisison tomography; grant from NWO: VIDI 016.066.309 (J Mourik, F van Velden, R Boellaard; dept of nuclear medicine & PET research).

4. Bridgehead labelling; grant from NWO STW (VUmc investigator: JDM Herscheid; dept of nuclear medicine & PET research).

5. Accuracy of 18FDG-PET and spiral CT for the early prediction of non-response to preoperative chemoradiotherapy in patients with esophageal cancer (NEOPEC); multicentre prospective observational study; grant from ZON-MW 945-04-510 (VUmc investigators: R Boellaard, EF Comans, M Cuesta, OS Hoekstra; depts of nuclear medicine & PET research and surgical oncology).

6. 18FDG-PET for avoidance of futile direct laryngoscopies under general anaesthesia with taking of biopsies in patients with suspicion on recurrent laryngeal carcinoma after radiotherapy (RELAPS); multicentre prospective observational study; grant from ZON-MW no. 945-04-311 (VUmc investigators: L van der Putten, R de Bree, EFI Comans, C Uyl-de Groot, M Boers, CR Leemans; depts of nuclear medicine & PET research, otolarynogology and clinical epidemiology & biostatistics).

7. Nanobodies tegen tumoren en neurodegeneratieve ziekten; grant from Ablynx (GAMS van Dongen; depts of otolaryngology and nuclear medicine & PET research).

8. Synthesis and evaluation in tumor bearing mice of [18F]ML10 as a potential PET imaging ligand for apoptosis; collaboration with NST Neurosurvival Technologies, Israel (AD Windhorst, GAMS van Dongen; dept of nuclear medicine & PET research).

9. 11C docetaxel in oncology; grant from Treucom/SBGO (NH Hendrikse, OS Hoekstra, AA Lammertsma; dept of nuclear medicine & PET research).

10. 18FDG PET response evaluation of chemoradiation in pancreatic cancer (PANTAR); grant from Roche, single centre observational study (B van Triest, B Kunnen, OS Hoekstra; depts of radiation therapy, medical oncology and nuclear medicine & PET research).

11. FDG and H215O PET response evaluation in lung cancer (bT); grant from Roche,

multicentre observational study (EF Smit, OS Hoekstra; depts of pulmonology and nuclear medicine & PET research).

12. Preventie en vroegdiagnostiek van prostaatkanker: de toepassing van groeisignaal-evaluatie voor de voorspelling van tumor gedrag; grant from CCA (postcode-loterij); (RJA van Moorselaar, AA Geldof; depts of nuclear medicine & PET research and urology).

13. Evaluation of [C-11]R116301 as a tracer for in vivo quantification of NK1 receptors in human subjects; Clinical Study Agreement with Johnson&Johnson Pharmaceuticals, L.L.C. North


Brunswick (SPA Wolfensberger, AJ Airaksinen, BNM van Berckel, R Boellaard, DJ Veltman, AD Windhorst, JE Leysen, AA Lammertsma).

iii. Publications During the period 2004-2005 members of the Department of Nuclear Medicine & PET research authored or co-authored some 100 papers, which appeared in international peer reviewed journals. In addition, four PhD theses were published. A complete list of published national and international papers is given under References. iv. Patents Herscheid JDM, Verbeek J – Bridgehead labelled radiopharmaceuticals – EP patent 05075259.1, 2005 v. Awards 1. P Verboom et al. EANM Springer award best clinical paper (2004) 2. NM Bruin et al. EANM Springer award best scientific paper Technology (2004) 3. CM van Rij. Winner Woldring Prijs 2004 (NVNG) for best scientific presentation. vi. Invited talks (international) 1. Boellaard R. Influence of the decay spectrum on the quantification of “Dirty Isotopes”;

First symposium “124-I in biological and medical application”, September 30 – October 1, 2005, Essen, Germany.

2. Geldof AA. Gossypol enhances radiation effects in human prostate cancer cells; 9th Int Wolfsberg Meeting, June 18-20, 2005, Ermatingen, Switserland.

3. Hoekstra OS. Towards valid markers of response: the EORTC experience; NCI Workshop on The Role of FDG PET in the Evaluation of Therapeutic Response in Cancer, January 10-11, 2005, Washington DC, USA.

4. Hoekstra OS. EORTC laboratory research groups: activities, aims and objectives of the functional imaging group; 25th Winter meeting of the EORTC – Pharmacology and Molecular Mechanisms Group, January 28-31, 2004, Bradford, UK.

5. Hoekstra OS. Towards valid markers of response: the case of PET; Annual Meeting of the European Society of Radiotherapy, October 24-28, 2004, Amsterdam, Netherlands.

6. Hoekstra OS. Should a PET scan be a requirement for optimal cancer management? Annual Meeting of the European Society of Medical Oncology, October 29 – November 2, 2004, Vienna, Austria.

7. Hendrikse NH. Visualization of physiological functions – imaging of P-glycoprotein transport with positron emission tomography (PET); First International Symposium on Resistant Cells “To die or not to die, is that resistant?”, May 6, 2005, Gwanju, South Korea.

8. Lammertsma AA.. Role of human and animal PET studies in drug development; International Workshop on Quantitation in Biomedicel Imaging with PET and MRI, January 26-27, 2004, Osaka, Japan.


9. Lammertsma AA. Technological developments of fusion imaging; PET and Fusion (CT) Imaging in Cardiology: Diagnostic and Clinical Perspectives; February 19-20, 2004, London, UK.

10. Lammertsma AA. Qualitative and quantitative analyses; NCI Workshop on the Role of FDG PET in the Evaluation of Therapeutic Response in Cancer, January 10-11, 2005, Washington DC, USA.

11. Lammertsma AA. Dedicated brain scanners – opportunities and pitfalls; X Turku PET Symposium, May 28-31, 2005, Turku, Finland.

12. Lammertsma AA. Dedicated brain scanners: opportunities and pitfalls; Towards a next generation of high-resolution PET scanners, September 29-30, 2005, Delft, The Netherlands.

13. Lammertsma AA. Methods for definition of regions of interest and statistical models for the brain; Annual Congress of the European Association of Nuclear Medicine, October 15-19, 2005, Istanbul, Turkey.

14. Lammertsma AA. How should we analyse FDG-PET studies for monitoring tumor response? Workshop Biological Imaging for Therapy Selection and Tumor Response Monitoring, December 3, 2005, München, Germany.

15. Lubberink M. Quantitative positron emission tomography for drug development and imaging treatment response – requirements and pitfalls; 26th Winter meeting of the EORTC – Pharmacology and Molecular Mechanisms Group, January 26-29, 2005, Arcachon, France.

16. Molthoff CFM. Ovarian cancer and MOv18: the Amsterdam experience; what did we learn? Clinical Advisory Meeting Morphotec Inc., March 22-24, 2004, Philadelphia, USA.

17. Molthoff CFM. Early assessment of response to chemotherapy in breast cancer using positron emission tomography; The Susan G. Komen Breast Cancer Foundation’s eighth Annual Mission Conference, A Promise in Action, June 5-7, 2005, Washington DC, USA.

18. Molthoff CFM. Biological correlates of [18F]FDG uptake in cancer; Fourth Annual Meeting of the Society of Molecular Imaging; September 7-10, 2005, Cologne, Germany.

19. Pijpers R. Sentinel node in head and neck cancer; Annual Congress of the European Association of Nuclear Medicine, October 15-19, 2005, Istanbul, Turkey.

20. Schuitemaker A. Imaging of inflammatory processes in MCI-patients. Annual Congress of the European Association of Nuclear Medicine, October 15-19, 2005, Istanbul, Turkey.

vii. International collaborations Listed are those international collaborations that have resulted in a joint publication in 2004 or 2005, or that involved a visit of at least one month during the same period. 1. Van Berckel BNM – Laruelle M, Columbia University, New York, USA. 2. De Jong HWAM, Boellaard R – Wienhard K and co-workers, Max Planck Institute for

Neurologische Forschung, Cologne, Germany. 3. De Jong HWAM – Lenox M and co-workers, CPS Molecular Imaging, Knoxville, TN, USA. 4. De Jong HWAM, Lammertsma AA – Collaboration within a network of 14 PET groups in

Europe and North America to perform a multi centre HRRT performance investigation. 5. Lammertsma AA – Hatazawa J, Maruyama K, Osaka University, Osaka, Japan. 6. Lammertsma AA, van Berckel BNM, Boellaard R, Lubberink M, Kropholler M,

Schuitemaker A – EC concerted action “Neuroreceptor changes in mild cognitive impairment”, together with groups from Copenhagen, Stockholm, Uppsala and Naples.

7. Lammertsma AA, Boellaard R – Cammici PG, Rimoldi O, Medical Research Council Clinical Sciences Centre, London, UK

8. Lammertsma AA, Boellaard R – Schäfers KP, University of Münster, Münster, Germany.


9. Lammertsma AA, Boellaard R, Lubberink M – Jones T, Price P, Rajasekharan S, Manchester Molecular Imaging Centre, Manchester, UK.

10. Lubberink M – Lundqvist H, Sandström M, Uppsala University and Uppsala University Hospital, Uppsala, Sweden.

11. Lubberink M – Bergström M, Razifar P, Uppsala University and Uppsala Imanet AB, Uppsala, Sweden.

12. Molthoff CFM – Herlyn D, Wistar Institute, Philadelphia, USA. 13. Molthoff CFM – Enger PO, Neuro Oncology, University of Bergen, Bergen, Norway. 14. Windhorst AD – Eisenhut M, DKFZ Heidelberg, Germany.


VIII. Societal impact Many members of the Department of Nuclear Medicine & PET Research are active in supporting scientific progress with respect to nuclear medicine and in implementing novel nuclear medicine technology into routine patient care. i. Development of guilines The final step following evaluation of a diagnostic technology is the development of guidelines for its proper use. Keeping in line with the mission of the department, several of its members of staff were actively engaged in this activity, usually following a mandate from their professional society. In recent years, the development of guidelines has switched from consensus to evidence based procedures. This is an important step forward, but it also is more demanding for the professionals involved in drafting these guidelines. In the period 2004-2005, three national CBO (Dutch Institute for Healthcare Improvement) guidelines with active contributions from members of the department were published:

1. Richtlijn Niet-Kleincellig longcarcinoom: stadiëring en behandeling. 2004, uitg. van Zuiden, Alphen a/d Rijn (VUmc: OS Hoekstra).

2. Richtlijn Non-Hodgkin Lymfoom. 2004, uitg. van Zuiden, Alphen a/d Rijn. (VUmc: OS Hoekstra).

3. Behandeling van het mammacarcinoom. 2005, uitg. van Zuiden, Alphen a/d Rijn (VUmc: R Pijpers).

Moreover, members of the department directly participated in the development of guidelines on diagnosis and management of hepatic metastases (VUmc: EFI Comans), and indirectly to the one on esophageal cancer (for which GWM Sloof, AMC, was the NVNG delegate). The knowledge on quantitative PET methodology was actively disseminated (other than by publications) by Boellaard, as member of the NVNG/NVKF joint committee “Acceptatietesten en kwaliteitscontrole van PET camera’s”. ii. Member expert committees The Dutch Cancer Foundation KWF installed a multidisciplinary committee to explore future scenarios with respect to cancer imaging. The final report (Signaleringscommissie KWF. Beeldvormende technieken binnen de kankerbestrijding: Vizier op de toekomst; Van den Boogaard, Oisterwijk, 2005; VUmc: OS Hoekstra) included an outlook which accounted for epidemiological as well as technological trends. To finalize the topdown round and to wrap up the current position of PET in the Netherlands, ZON-MW installed a working party, of which OS Hoekstra is a member. The Netherlands Heart Foundation installed an expert committee to investigate the (potential) role of imaging techniques in cardiovascular diseases and the need for further research. The final report (Image guided strategies in cardiovascular disease; VUmc participant: AA Lammertsma) will appear in 2006.

iii. Organisation of courses, meetings and workshops 1. Lammertsma AA, van Berckel BNM, Boellaard R, Veltman DJ. Organisers XXIInd

International Symposium on Cerebral Blood Flow, Metabolism, and Function & VIIth


International Conference on Quantification of Brain Function with PET, June 7-11, 2005, Amsterdam, Netherlands.

2. Lammertsma AA. Co-organiser PET pharmacokinetic course 2005, June 12-14, 2005, Groningen, Netherlands.

3. Boellaard R. Co-organiser NVKF workshop Acceptatietesten en kwaliteitscontrole van PET camera’s, 2005.

4. Comans EF, Hoekstra OS. Organisers eight post-graduate courses on PET in oncology for nuclear medicine physicians.

5. Comans EF, EF Smit, F Verzijlbergen, Hoekstra OS. Organisers NVALT national post-graduate course on PET in lung cancer for pulmonologists, 2005, Ede, Netherlands.

6. De Jong HWAM. Co-organiser KLIFOP Fysicadag, November, 12, 2004, Rotterdam, Netherlands.

7. Windhorst AD. Co-organiser national radiochemistry collaborative workshop, Zelhem, Netherlands.

8. Windhorst AD, Lammertsma AA. Organisers LACDR Workshop PET in drug development: feasibility, utility and prerequisites, November 21, 2005, Amsterdam, Netherlands.

iv. Editor or member editorial board international scientific journals AA Geldof Journal of Cancer Research and Clinical Oncology (Editorial board) JDM Herscheid Letters in Drug Design & Discovery (Editorial board) OS Hoekstra The Oncologist (Section editor imaging) AA Lammertsma NuklearMedizin (Section editor medical physics & radiation protection) Journal of Cerebral Blood Flow and Metabolism (Deputy Chief-Editor) Molecular Imaging and Biology (International associate editor)

European J of Nuclear Medicine and Molecular Imaging (Editorial board) Current Medical Imaging Reviews (Editorial board) Drug Discovery Today: Technologies (Guest editor) v. Member national and international scientific organisations Boellaard R -Member joint committee “Acceptatietesten en kwaliteitscontrole van PET camera’s”, Dutch

Society of Nuclear Medicine (NVNG) and Dutch Society of Clinical Physics (NVKF) Bruin N -Member quality registration committee Dutch Society for Medical Imaging and Radiotherapy

(NVMBR) Comans EF -Board member Dutch Society of Nuclear Medicine (NVNG) -Board member Dutch Society for Oncology (NVVO) -Member education renewal committee, Dutch Society of Nuclear Medicine (WEMONG,

NVNG)


Hendrikse NH -Board member Post Universitair Onderwijs Ziekenhuisapothekers (PUOZ) -Board member Dutch Society of Nuclear Medicine (NVNG) Herscheid JDM -Member Scientific Council, Leiden/Amsterdam Centre for Drug Research Hoekstra OS -Member EORTC Translational research advisory committee (TRAC) -Board member EORTC PAMM group -Member ZON-MW VEMI (Vroege Evaluatie Medische Innovaties) committee De Jong HWAM -Board member Medical Physics Trainees (Klifop, NVKF) -Member council, Dutch Society of Clinical Physics (Concilium, NVKF) -Member educational committee, Dutch Society of Nuclear Medicine (OnderwijsCie, NVNG) De Jong-Greuter CSM -Member training committee Dutch Society for Medical Imaging and Radiotherapy (NVMBR) -Member educational committee Dutch Society for Medical Imaging and Radiotherapy

(SOANG/NVMBR) Lammertsma AA -Director International Society for Cerebral Blood Flow and Metabolism -Member IFAC BIOMED technical committee -Board member Dutch Commission on Radiation Dosimetry (NCS) -Board member Dutch Society of Clinical Physics (NVKF) -Board member section nuclear medicine, Dutch Society of Clinical Physics (kring KFNG,

NVKF) -Chairman Executive Committee for Board Registration, Dutch Society of Clinical Physics

(TCie, NVKF) Van Lingen A -Member committee for scientific meetings, Dutch Society of Nuclear Medicine (NVNG) -Member plenary visitation committee, Dutch Society of Nuclear Medicine (NVNG) Molthoff CFM -Member Dutch working group “Advanced Drug Delivery/Drug Targeting” of the Netherlands

Society of Immunology, Netherlands Institute of Biology, and Netherlands Society for Pharmaceutical Science

Pijpers R -Chairman educational committee Dutch Society of Nuclear Medicine (OnderwijsCie, NVNG) De Vries T -Coordinator benchgroups nuclear medicine in the Netherlands (except eastern part of the country) Windhorst AD -Board member Radiochemie.nl


IX. Current trends and perspectives i. Organisational structure The reorganisation of the Department of Nuclear Medicine & PET Research, following its formation in January 2004, was a lengthy process, requiring participation of all members of the department. Functioning of a department, however, does not only depend on defining an appropriate and functioning organisational structure, but more on the motivation of its members to work together as a team. This will require constant attention in the coming years, especially as the department is spread out over four different locations on the VU campus. This dispersion of activities and people will further increase in 2006, as the installation of the PET/CT scanner involves moving a large number of staff to another two locations. Clearly, this is far from ideal for a multidisciplinary department, where communication between disiplines is extremely important. The latter condition has been the main reason for forming sections, for appointing section heads and coordinators within sections, and for setting up a meeting structure in which there is regular discussion of progress, both within and between sections. These measures will be monitored throughout the next year and, when appropriate, adjustments will be made. Based on the general spirit after the new structure was in place, however, it is very unlikely that major changes are needed. Nevertheless, it will be necessary to pursue better housing facilities for the department, even if this can not be achieved in the near future, because of the general housing problems of VUmc. As mentioned earlier, the department created a new chair in radiopharmacochemistry in collaboration with the Faculty of Sciences and BV Cyclotron VU. Unfortunately, the search for an appropriate candidate for this post was not successful. Continuity of the work of the chemistry section has been guaranteed by appointing prof. van Dongen as acting head of section. This is, however, a temporary solution and the search for an appropriate candidate will be initiated again in about two years time. ii. Patient care In 2006, the negotiations for setting up a nuclear medicine facility in the Amstelland Hospital, Amstelveen will be finalised, and it is expected that this service will be opened early 2007. This site will be run by the department of Nuclear Medicine & PET Research. This initiative is in line with a general agreement of collaboration between the two hospitals. The Cancer Centre Amsterdam (especially upon the instigation of prof. HM Pinedo) has made it possible for the department to purchase a state-of-the-art PET-CT scanner. Prolonged procedures proved necessary to allocate appropriate housing facilities within the VUmc site of the department. Initially, this scanner should have been installed sometime in 2005. However, as mentioned, space allocation problems were considerable, as its installation required not only moving offices and laboratories, but also reenforcing the floor of the projected PET-CT room (5th floor of the hospital). At present, it is expected that installation will take place at the end of 2006. It is foreseen that PET-CT is the first of an array of new technological developments aimed at improving science as well as patient management, often by combining the best of the different domains of diagnostic medicine. As such, academic centres are excellent laboratories for exploration of the multidisciplinary interaction that should be the basis for real progress. Therefore, at the VUmc, PET-CT is likely to intensify the bonds between radiology, nuclear medicine & PET research and radiotherapy. These three departments also have in common that


they use radioactivity in a setting of advanced and expensive equipment, and that they participate in a shared technologist training programme. iii. Education and professional training It is foreseen that PET(-CT) is rapidly diffusing throughout the Netherlands, with an estimated number of scanners of one per 500.000 inhabitants by 2007. Experience obtained with the technology assessment program (2000-present), the generally acknowledged lack of training facilities within The Netherlands, and the very positive feedback of the participants who have followed one of the post-graduate courses organised by the department, have been the main reasons for extending the post-graduate teaching programme. This will be carried out in close collaboration with others (VUmc medical specialists and third parties). iv. Research There is growing recognition that PET can play an important role in drug development, as it is able to demonstrate efficacy of therapy in a non-invasive manner. At present, there is growing interest in defining the role of PET in both preclinical and clinical studies. As a result some large pharmaceutical companies invest in their own PET centres or they seek strategic collaborations with academic centres. The collaboration between academic PET centres and pharmaceutical industries is by no means one-way traffic. Knowledge within pharmaceutical industries can be an important factor in developing new PET tracers. The Department of Nuclear Medicine & PET Research therefore has an open mind in the interaction with industry. In the years 2004 and 2005, the department had ongoing collaborations with a number of industries (e.g. Boehringer Ingelheim, Tyco/Mallinckrodt, Johnson & Johnson, IBA Molecular, Schering, Philips, Ablynx, Aventis, Macrocyclics and CPS Molecular Imaging) for, amongst others, the development and application of molecular imaging. These cover the whole range of collaboration possibilities, from a custom radiolabelling service to an interactive collaborative approach in the development of methodology. Following the merger of RNC, Department of Nuclear Medicine and PET project, this range of activities nicely fits within the present multidisciplinary setting of the VUmc department of Nuclear Medicine & PET Research, and in fact a number of projects are anticipated for the coming years. At the same time, the department will also maintain a positive attitude towards collaboration with other academic centres of excellence, in an attempt to make efficient use of the limited (worldwide) expertise and facilites for quantitative PET.


X. Personnel The formation of sections was part of the reorganisation process. They came into force during 2005. To better illustrate the expertise of the members of staff, the list below shows a listing by section. An asterisk denotes that the discipline does not constitute a formal section within the department. On march 23rd, 2005, Mrs. Ban Tony, MD, one of our nuclear medicine residents, died after a prolonged illness. With her, we have lost a warm-hearted, appreciated and hard-working colleague. i. Heads of Department

Prof. O.S. Hoekstra, MD, PhD, clinical (from 1 September, 2004) Prof. A.A. Lammertsma, PhD, research Prof. G.J.J. Teule, MD, PhD, clinical (until 1 September, 2004)

ii. Scientific Staff Biology W.G.E. Direcks, MSc M. van Gelder, BSc A.A. Geldof, PhD F.J.P.M. van Kan, MSc (until 1 October, 2004)

Prof. A.A. Lammertsma, PhD, section head C.F.M. Molthoff, PhD, coordinator biology N. Proost, BSc (from 1 April, 2005) Chemistry

A.J. Airaksinen, PhD (until 1 January, 2005) J. Brinkhorst, BSc (from 1 February, 2005) Prof. G.A.M.S. van Dongen, PhD, section head (from 1 January, 2006) J.L.H. Eersels, MSc H.N.J.M. Greuter J.D.M. Herscheid, PhD, coordinator basic radiochemistry P.J. Klein, BSc R.P. Klok, BSc G. Luurtsema, BSc, coordinator metabolite analysis M.P.J. Mooijer, BSc P.L.B. van Ophemert R.C. Schuit, BSc K. Takkenkamp, BSc E.W. van Tilburg, PhD J. Verbeek, BSc R.T. Versteegh, BSc G.W.M. Visser, PhD A.D. Windhorst, PhD, coordinator PET tracer development and production

Instrumentation

F.L. Buijs J.F. Keus A. de Nooij


L.F. van Rooij, section head P.E. Schollema R.P. van der Valk

Medicine (section diagnostics & therapy)

B.N.M. van Berckel, MD, PhD, coordinator neuroPET E.F.I. Comans, MD, PhD, coordinator whole body PET Prof. O.S. Hoekstra, MD, PhD, section head H.J. Pijpers, MD, PhD, coordinator conventional nuclear medicine P.G.H.M. Raijmakers, MD, PhD J.C. Roos, MD, PhD (until 1 June, 2004) Prof. G.J.J. Teule, MD, PhD (until 1 September, 2004) A. van Schie, MD (fellow from 1 September, 2004) Resident nuclear medicine physicians

M. Akarriou, MD (from 1 December, 2002) C.J. Hoekstra, MD, PhD (until 1 October, 2005)

A.B. van Dijk, MD, (extension as part-time fellow until 1 May, 2005) R.J. Kooistra, MD, (until 1 April, 2005) S.N.F. Rizvi, MD, (from 1 January, 2005)

A. van Schie, MD (until 1 September, 2004) S.A. Srbljin, MD, (from 1 November, 2004)

J. Tim, MD, (from 1 January, 2004) B.N. Tony, MD, (†23 March, 2005) I.A.C. Rutten-Vermeltfoort, MD (from 1 January, 2003) N.R.L. Wagenaar, MD, (from 1 September 2004)

Nuclear Medicine Technology

S.C.M. van Balen, BSc, coordinator PET N.M. Bruin, BSc E. Guijt, BSc C.S.M. de Jong-Greuter, BSc F. Jongsma, BSc R.H.A. Koopmans, BSc J.H. van Mourik G.D. Mulder, BSc J.M.L.H. Versteeg-Fontein, BSc T. de Vries, BSc, section head, coordinator conventional nuclear medicine A.M. de Wildt, BSc Trainees A.Beemster (from 16 February, 2004, until 9 September, 2004) S. Brunke (from 9 February, 2004, until 3 April, 2004)

M.J. Hartman (until 31 January, 2004) T. van Kassel (from 10 November, 2003, until 3 January, 2004) A.A. van de Ruit (from 1 September, 2004, until 1 January, 2005) M.D. van Santen (until 25 July, 2005)

Physics

R. Boellaard, PhD, coordinator PET physics H.W.A.M. de Jongh, PhD R.W. Kloet M.A. Kropholler. MSc


Prof. A.A. Lammertsma, PhD, section head A. van Lingen, PhD, coordinator conventional nuclear medicine physics M. Lubberink, PhD C.T. Mesina, MSc (until 1 July, 2004) M.M. Yaqub, MSc (from 19 February, 2004) F.H.P. van Velden, MSc (from 1 December, 2005)

*Medical, other

J. Emmering, MD A. Schuitemaker, MD Prof. D.J. Veltman, MD, PhD (psychiatrist) J.M. Zijlstra-Baalbergen, MD (hematologist) Medical student A.A.M. van der Veldt

*Pharmacology Prof. J.J. Leysen, PhD (from 1 November, 2004)

*Radiopharmacy E.J.F. Franssen, PharmD, PhD (until 1 June, 2004) N.H. Hendrikse, PharmD, PhD (from 1 February, 2005)

*Operational office C.H. Bakker (until 1 November, 2005) J.L. Boesten J.E. Handgraaf C. Karga (until 1 October, 2004) A.J.P. Kroonenberg-Kalwij J.C.G. van der Kuij A. van Lingen, PhD, head of operational office, chief radiation health officer C.G.A. Mascini-Heres diddens S.T.M. Schröder M.C. Stolker-Bouknecht J.J. van Veluwen, acting head patient administration (from 1 October, 2005) R.T. Versteegh, BSc T. Weijer M.M. Wiegman, BSc, head radiation safety officer (RNC site)

iii. PhD students PhD students are listed per research institute. As some projects had a link with both ICEN and LACDR, they have been put together. Where appropriate, collaboration with other departments or external institutes is indicated. The following abbreviations are used: AMC: Academic Medical Centre

UL: University of Leiden UMCG: University Medical Centre Groningen

UMCU: University Medical Centre Utrecht Finally, PhD students are divided into different categories: A – graduation and work prepared at VUmc B – graduation at VUmc, work prepared elsewhere C – graduation elsewhere, work prepared at VUmc D – graduation and most of the work performed elsewhere


ICEN & LACDR

1. L.I. Arwert (+endocrinology, cat A) 2. A.L. Bartels (+UMCG, cat D) 3. J.P. Bremmer (+UMCU, cat D) 4. H. Folkersma (+neurosurgery, cat A) 5. S.G. Geuze (+UMCU, cat C/D) 6. O.A. van den Heuvel (+psychiatry, cat A) 7. U.M.H. Klumpers (+psychiatry, cat A) 8. M.A. Kropholler (cat A) 9. L.C. Liefaard (+UL, cat C/D) 10. G. Luurtsema (cat A) 11. M.L. van der Meer (+neurology, cat A) 12. C.T. Mesina (cat A) 13. M.M. Ponsen (+neurology, cat A) 14. A. Schuitemaker (+neurology, cat A) 15. N. Tolboom (+neurology, cat A) 16. F.H.P. van Velden (cat A) 17. N.C.C. Vulink (+UMCU, cat C/D) 18. S.P.A. Wolfensberger (+psychiatry, cat A) 19. M.M. Yaqub (cat A)

V-ICI

1. P. Borjesson (+otolaryngology, cat A) 2. J. Brouwer (+otolaryngology, cat A) 3. W.G.E. Direcks (cat A) 4. E.H. Elzinga (+rheumatology, cat A) 5. J. Emmering (+medical oncology, cat A) 6. G.J.M. Herder (+pulmonology; cat A) 7. J.J.M. van der Hoeven (cat A) 8. L. Hooft (+clinical epidemiology&biostatistics, cat A) 9. B.M. Klabbers (+radiotherapy, cat A) 10. N.C. Krak (+medical oncology, cat A) 11. A.J. de Langen (+pulmonology/surgery, cat A) 12. U. Joshi (cat A) 13. J.M.T. Omloo (+AMC, cat D) 14. L. van der Putten (+otolaryngology, cat A) 15. A. Senft (+otolaryngology, cat A) 16. H. van Tinteren (+clinical epidemiology&biostatistics, cat A) 17. O.J. Visser (+haematology, cat A) 18. M.J. Vos (+neurology, cat A) 19. M. Westerterp (+AMC, cat D) 20. M. van Wondergem (+haematology, cat A) 21. J.M. Zijlstra-Baalbergen (+hematology; cat A)

ICaR-VU

1. P.A. Dijkmans (+cardiology, cat A) 2. T. Hendriks (+cardiology, cat C/D) 3. P. Knaapen (+cardiology, cat A) 4. A. Rijbroek (+surgery, cat A) 5. L.J. Rijzewijk (+endocrinology, cat A)


6. I.A.C. Vermeltfoort (cat A) 7. M. Vervloet (+nephrology, cat A) 8. A. van der Weerdt (+cardiology, cat A)

MOVE

1. O.P.P. Temmerman (+orthopaedics, cat A) 2. F. Vermaat (+surgery, cat A)


XI. References i. Dissertations 2004: JJM van der Hoeven. Prospects for positron emission tomography in the staging and treatment of breast cancer patients. (Co-) promotors Prof Dr GJJ Teule, Prof Dr S Meijer, Dr OS Hoekstra (cat A). 2005: MJ Vos. Evaluation of response, toxicity and outcome in glioma therapy. (Co-) promotors Prof Dr JJ Heimans, Prof Dr W Vandertop, Dr Tj Postma, Dr OS Hoekstra (cat A). 2005: L Hooft. Molecular imaging in rare diseases: the case of thyroid cancer and positron emission tomography. Print Partners Ipskamp, Amsterdam. 143 p. ISBN 90-9019542-4. (Co-) promotors: Prof dr M Boers, Prof dr GJJ Teule, Dr OS Hoekstra, Dr MW van Tulder (cat A). 2005: OA van den Heuvel. Neuroimaging in obsessive-compulsive and related disorders: investigation of the frontal-striatal and limbic circuits. (Co-) promotors Prof Dr R van Dyck, Prof Dr AA Lammertsma, Dr HJ Groenewegen, Dr DJ Veltman (cat A). cum laude ii. International peer reviewed papers Admiraal GC, Schie van A, Meyel van JJM, Vasmel WLE. Giant Liver Hemangioma in 3 sisters. J Gastroenterol Hepatol 2004; 19:344-345. Annema JT, Hoekstra OS, Smit EF, Veselic M, Versteegh MI, Rabe KF. Towards a minimally invasive staging strategy in NSCLC: analysis of PET positive mediastinal lesions by EUS-FNA. Lung Cancer 2004; 44:53-60. Arwert L, Roos JC, Lips P, Twisk JWR, Manoliu RA, Drent ML. Effects of 10 years of growth hormone (GH) replacement therapy in adult GH-deficient men. Clin Endocrinol (Oxf) 2005; 63:310-316. Arwert LI, Veltman DJ, Deijen JB, Lammertsma AA, Jonker C, Drent ML. Memory Performance and the Growth Hormone/Insulin-Like Growth Factor Axis in Elderly: A Positron Emission Tomography Study. Neuroendocrinology 2005; 81:31-40. Bipat S, van Leeuwen MS, Comans EF, Pijl ME, Bossuyt PM, Zwinderman AH, Stoker J. Colorectal liver metastases: CT, MR imaging, and PET for diagnosis - meta-analysis. Radiology 2005; 237:123-131. Blokhuis TJ, van der Schaaf MC, van den Tol MP, Comans EF, Manoliu RA, van der Sijp JR. Results of radio frequency ablation of primary and secondary liver tumors: long-term follow-up with computed tomography and positron emission tomography-18F-deoxyfluoroglucose scanning. Scand J Gastroenterol Suppl 2004; 241:93-97. Boellaard R, Krak NC, Hoekstra OS, Lammertsma AA. Effects of noise, image resolution, and ROI definition on the accuracy of standard uptake values: a simulation study. J Nucl Med 2004; 45:1519-27.


Boellaard R, van Lingen A, van Balen SC, Lammertsma AA. Optimization of attenuation correction for positron emission tomography studies of thorax and pelvis using count-based transmission scans. Phys Med Biol 2004; 21; 49:N31-N38. Boellaard R, Knaapen P, Rijbroek A, Luurtsema GJ, Lammertsma AA. Evaluation of basis function and linear least squares methods for generating parametric blood flow images using 15O-water and positron emission tomography. Mol Imaging Biol 2005; 7:273-285. Börjesson P, Postema E, de Bree R, Roos JC, Leemans C, Kairemo K, van Dongen G. Radioimmunodetection and radioimmunotherapy of head and neck cancer. Oral Oncol 2004; 40:761-772 . Borst GR, Belderbos JS, Boellaard R, Comans EF, De Jaeger K, Lammertsma AA, Lebesque JV. Standardised FDG uptake: a prognostic factor for inoperable non-small cell lung cancer. Eur J Cancer 2005; 41:1533-1541. Bravenboer N, Holzmann PJ, ter Maaten JC, Stuurman LM, Roos JC, Lips P. Effect of long-term growth hormone treatment on bone mass and bone metabolism in growth hormone-deficient men. Bone Miner Res 2005; 20:1778-1784. Brouwer J, Bodar EJ, De Bree R, Langendijk JA, Castelijns JA, Hoekstra OS, Leemans CR. Detecting recurrent laryngeal carcinoma after radiotherapy: room for improvement. Eur Arch Otorhinolaryngol 2004; 261:417-422. Brouwer J, de Bree R, Comans EF, Castelijns JA, Hoekstra OS, Leemans CR. 18FDG PET in the clinically negative neck: is it likely to be superior? Eur Arch Otorhinolaryngol 2004; 261:479-483. Brouwer J, de Bree R, Hoekstra OS, Golding RP, Langendijk JA, Castelijns JA, Leemans CR. Screening for distant metastases in patients with head and neck cancer: is chest computed tomography sufficient? Laryngoscope 2005; 115:1813-1817. Brouwer J, Bree R, Hoekstra OS, Langendijk JA, Castelijns JA, Leemans CR. Screening for distant metastases in patients with head and neck cancer: what is the current clinical practice? Clin Otolaryngol 2005; 30:438-443. Van Dongen GA, Visser GW, Vrouenraets MB. Photosensitizer-antibody conjugates for detection and therapy of cancer. Adv Drug Deliv Rev 2004; 56:31-52. Eersels JL, Klok RP, Verbeek J, Jonker AJ, Herscheid JD. Synthesis and evaluation of radiolabeled analogs of the antidepressant drug zimelidine as potential SPECT-ligands for the serotonin transporter. Nucl Med Biol 2004; 31:563-569. Eersels JLH, Travis MJ, Herscheid JDM. Manufacturing I-123 labelled radiopharmaceuticals. Pitfalls and solutions. J Label Compd Radiopharm 2005; 48:241-257. Engelbregt MJ, van Weissenbruch MM, Lips P, van Lingen A, Roos JC, Delemarre-van de Waal HA. Body composition and bone measurements in intra-uterine growth retarded and early postnatally undernourished male and female rats at the age of 6 months: comparison with puberty. Bone 2004; 34:180-186.


Fabry HF, Mutsaers PG, Meijer S, Torrenga H, Pijpers R, van Leeuwen PAM, van der Sijp J. Clinical relevance of parasternal uptake in sentinel node procedure for breast cancer. J Surg Oncol 2004; 87:13-18. De Geus-Oei LF, van Eerd-Vismale J, Molthoff C, Corstens F, Oyen W, Boerman O. Tracers to monitor the response to chemotherapy: in vitro screening of four radiopharmaceuticals. Cancer Biother Radiopharm 2004; 19:457-465. Greuter HN, van Ophemert PL, Luurtsema G, Franssen EJ, Boellaard R, Lammertsma AA. Validation of a multiwell gamma-counter for measuring high-pressure liquid chromatography metabolite profiles. J Nucl Med Technol 2004; 32:28-32.

Greuter HJNM, van Ophemert PLB, Luurtsema G, van Berckel BNM, Franssen EJF, Windhorst AD, Lammertsma AA. Optimizing an online SPE-HPLC method for analysis of (R)-[11C]1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide [(R)-[11C]PK11195] and its metabolites in man. Nucl Med Biol 2005; 32:307-312. Herder GJ, Golding RP, Hoekstra OS, Comans EF, Teule GJ, Postmus PE, Smit EF. The performance of 18F-fluorodeoxyglucose positron emission tomography in small solitary pulmonary nodules. Eur J Nucl Med Mol Imaging 2004; 31:1231-1236.

Herder GJ, van Tinteren H, Golding RP, Kostense PJ, Comans EF, Smit EF, Hoekstra OS. Clinical prediction model to characterize pulmonary nodules: validation and added value of 18F-fluorodeoxyglucose positron emission tomography. Chest 2005; 128:2490-2496.

Van den Heuvel OA, Veltman DJ, Groenewegen HJ, Dolan RJ, Cath DC, Boellaard R, Mesina CT, van Balkom AJ, van Oppen P, Witter MP, Lammertsma AA, van Dyck R. Amygdala activity in obsessive-compulsive disorder with contamination fear: a study with oxygen-15 water positron emission tomography. Psychiatry Res 2004; 132:225-237. Hoekstra CJ, Stroobants SG, Smit EF, Vansteenkiste J, van Tinteren H, Postmus PE, Golding RP, Biesma B, Schramel FJ, van Zandwijk N, Lammertsma AA, Hoekstra OS. Prognostic Relevance of response evaluation using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with locally advanced non-small-cell lung cancer. J Clin Oncol 2005; 23:8362-8370.

Van der Hoeven JJ, Krak NC, Hoekstra OS, Comans EF, Boom RP, van Geldere D, Meijer S, van der WE, Buter J, Pinedo HM, Teule GJ, Lammertsma AA. 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography in staging of locally advanced breast cancer. J Clin Oncol 2004; 22:1253-1259.

Hofman HA, Knaapen P, Boellaard R, Bondarenko O, Gotte MJ, van Dockum WG, Visser CA, van Rossum AC, Lammertsma AA, Visser FC. Measurement of left ventricular volumes and function with O-15-labeled carbon monoxide gated positron emission tomography: comparison with magnetic resonance imaging. J Nucl Cardiol 2005; 12:639-44. Hooft L, Hoekstra OS, Boers M, van Tulder MW, Van Diest P, Lips P. Practice, efficacy, and costs of thyroid nodule evaluation: a retrospective study in a Dutch university hospital. Thyroid 2004; 14:287-293.


Hooft L, van der Veldt AA, van Diest PJ, Hoekstra OS, Berkhof J, Teule GJ, Molthoff CF. [18F]fluorodeoxyglucose uptake in recurrent thyroid cancer is related to hexokinase I expression in the primary tumor. J Clin Endocrinol Metab 2005; 90:328-334.

De Jong HWAM, Boellaard R, Lenox M, Michel C, Lammertsma AA. Correction for emission contamination in transmission scans for the High Resolution Research Tomograph. IEEE Trans Nuclear Science, 2004; 51:673-676.

Joshi U, Hoekstra OS, Boellaard R, Comans EF, Raijmakers PG, Pijpers RJ, Miller SD, Teule GJ, van Lingen A. Initial experience with a prototype dual-crystal (LSO/NaI) dual-head coincidence camera in oncology. Eur J Nucl Med Mol Imaging 2004; 31:596-598. Joshi U, van der Hoeven JJ, Comans EF, Herder GJ, Teule GJ, Hoekstra OS. In search of an unknown primary tumour presenting with extracervical metastases: the diagnostic performance of FDG-PET. Br J Radiol 2004; 77:1000-1006. Joshi U, Raijmakers PG, van Lingen A, Comans EF, Pijpers R, Teule GJ, Hoekstra OS. Evaluation of pulmonary nodules: comparison of a prototype dual crystal (LSO/NAI) dual head coincidence camera and full ring positron emission tomography (PET). Eur J Radiol 2005; 55:250-254.

Joshi U, van der Sluijs JA, Teule GJ, Pijpers R. Proteus syndrome: a rare cause of hemihypertrophy and macrodactyly on bone scanning. Clin Nucl Med 2005; 30:604-605. Kessels LW, Simsek S, Van Hattum AH, Stam F, Comans EF. Nodular fasciitis: an unexpected finding on computed tomography and positron emission tomography. Eur J Intern Med 2004; 15:183-185.

Knaapen P, Boellaard R, Gotte MJ, Dijkmans PA, van Campen LM, de Cock CC, Luurtsema G, Visser CA, Lammertsma AA, Visser FC. Perfusable tissue index as a potential marker of fibrosis in patients with idiopathic dilated cardiomyopathy. J Nucl Med 2004; 45:1299-1304. Knaapen P, van Campen LM, de Cock CC, Gotte MJ, Visser CA, Lammertsma AA, Visser, FC. Effects of cardiac resynchronization therapy on myocardial perfusion reserve. Circulation 2004; 110:646-651.

Knaapen P, van Dockum WG, Bondarenko O, Kok WE, Gotte MJ, Boellaard R, Beek AM, Visser CA, van Rossum AC, Lammertsma AA, Visser FC. Delayed contrast enhancement and perfusable tissue index in hypertrophic cardiomyopathy: comparison between cardiac MRI and PET. J Nucl Med 2005; 46:923-9. Knaapen P, Götte MJW, van Dijk J, de Cock CC, Allaart CP, Lammertsma AA, Visser FC. Cardiac resynchronization therapy: assessment of dyssynchrony and effects on metabolism. Future Cardiol 2005; 1:1-11. Knaapen P, Lammertsma AA, Visser FC. Enhancement of perfusion reserve by cardiac resynchronization therapy. Eur Heart J 2005; 26:1447-1448.

Krak NC, Hoekstra OS, Lammertsma AA. Measuring response to chemotherapy in locally advanced breast cancer: methodological considerations. Eur J Nucl Med Mol Imaging 2004; 31:S103-S111.


Krak NC, Boellaard R, Hoekstra OS, Twisk JW, Hoekstra CJ, Lammertsma AA. Effects of ROI definition and reconstruction method on quantitative outcome and applicability in a response monitoring trial. Eur J Nucl Med Mol Imaging 2005; 32:294-301. Kropholler MA, Boellaard R, Schuitemaker A, van Berckel BN, Luurtsema G, Windhorst AD, Lammertsma AA. Development of a tracer kinetic plasma input model for (R)-[11C]PK11195 brain studies. J Cereb Blood Flow Metab 2005; 25:842-851. Liefaard LC, Ploeger BA, Molthoff CF, Boellaard R, Lammertsma AA, Danhof M, Voskuyl RA. Population pharmacokinetic analysis for simultaneous determination of Bmax and KD in vivo by positron emission tomography. Mol Imaging Biol 2005; 18:1-11. Lodder MC, Lems WF, Ader HJ, Marthinsen AE, van Coeverden SCCM, Lips P, Netelenbos JC, Dijkmans BAC, Roos JC. Reproducibility of bone mineral density measurement in daily practice. Ann Rheum Dis 2004; 63:285-289. Lubberink M, Boellaard R, Van der Weerdt AP, Visser FC, Lammertsma AA. Quantitative comparison of AW-OSEM and FBP reconstruction in 2D and 3D dynamic cardiac 18F-FDG PET. J Nucl Med 2004; 45:2008-2015. Luurtsema G, de Lange EC, Lammertsma AA, Franssen EJ. Transport across the blood-brain barrier: stereoselectivity and PET-tracers. Mol Imaging Biol 2004; 6:306-318. Luurtsema G, Molthoff C, Schuit R, Windhorst A, Lammertsma A, Franssen E. Evaluation of R-[11C]-verapamil as PET tracer of P-glycoprotein function in the blood–brain barrier: kinetics and metabolism in the rat. Nucl Med Biol 2005; 32: 87-93. Mey M van der, Janssen CG, Janssens FE, Jurzak M, Langlois X, Sommen FM, Verreet B, Windhorst AD, Leysen JE, Herscheid JDM. Synthesis and biodistribution of [11C]R116301, a promising PET ligand for central NK1 receptors. Bioorg Med Chem 2005; 13:1579–1586. Mijnhout GS, Riphagen II, Hoekstra OS. Update of the FDG PET search strategy. Nucl Med Commun 2004; 25:1187-1189. Moll AC, Hoekstra OS, Imhof SM, Comans EF, Schouten-van Meeteren AY, van der Valk P, Boers M. Fluorine-18 fluorodeoxyglucose positron emission tomography (PET) to detect vital retinoblastoma in the eye: preliminary experience. Ophthalmic Genet 2004; 25:31-35.

Nieuwenhuis EJ, van der Waal I, Leemans CR, Kummer A, Pijpers R, Castelijns JA, Brakenhoff RH, Snow GB. Histopathologic validation of the sentinel node concept in oral and oropharyngeal squamous cell carcinoma. Head Neck 2005; 27:150-158.

Noske DP, Peerdeman SM, Comans EF, Dirven CM, Knol DL, Girbes AR, Vandertop WP. Cerebral microdialysis and positron emission tomography after surgery for aneurysmal subarachnoid hemorrhage in grade I patients. Surg Neurol 2005; 64:109-115.

Van Oost FJ, van der Hoeven JJ, Hoekstra OS, Voogd AC, Coebergh JW, Van De Poll-Franse LV. Staging in patients with locoregionally recurrent breast cancer: current practice and prospects for PET. Eur J Cancer 2004; 40:1545-1553. Pasic A, Brokx HA, Comans EF, Herder GJ, Risse EK, Hoekstra OS, Postmus PE, Sutedja TG. Detection and staging of preinvasive lesions and occult lung cancer in the central airways


with 18F-fluorodeoxyglucose positron emission tomography: a pilot study. Clin Cancer Res 2005; 11:6186-6189.

Perk LR, Visser GWM, Vosjan MJWD, Stigter-van Walsum M, Tijink BM, Leemans CR, van Dongen GAMS. 89Zr as a PET surrogate radioisotope for scouting biodistribution of the therapeutic radiometals 90Y and 177Lu in tumor-bearing nude mice after coupling to the internalizing antibody cetuximab. J Nucl Med 2005; 46:1898-1906. Pijpers R, Buist MR, van Lingen A, Dijkstra J, van Diest PJ, Teule GJJ, Kenemans P, Verheijen RHM. The sentinel node in cervical cancer: scintigraphy and laparoscopic gamma probe-guided biopsy. Eur J Nucl Med Mol Imaging 2004; 31:1479-1486. Van Rij CM, Huitema ADR, Swart EL, Greuter HNJM, Lammertsma AA, van Loenen AC, Franssen EJF. Population plasma pharmacokinetics of 11C-flumazenil at tracer concentrations. Br J Clin Pharmacol 2005; 60:477-85. Van Royen BJ, Baayen JC, Pijpers R, Noske DP, Schakenraad D, Wuisman PI. Osteoid osteoma of the spine: a novel technique using combined computer-assisted and gamma probe-guided high-speed intralesional drill excision. Spine 2005; 30:369-373. Schins A, Van Kroonenburgh M, van Laere K, D'Haenen H, Lousberg R, Crijns H, Eersels J, Honig A. Increased cerebral serotonin-2A receptor binding in depressed patients with myocardial infarction. Psychiatry Research: Neuroimaging 2005; 139:155-163. Sminia P, Kuipers G, Geldof A, Lafleur V, Slotman B. COX-2 inhibitors act as radiosensitizer in tumor treatment. Biomed Pharmacother 2005; 59, Suppl 2:S272-S275. Sturkenboom M, Franssen E, Berkhof J, Hoekstra OS. Physiological uptake of 18FDG uptake in the neck and upper chest region: are there predictive characteristics? Nucl Med Commun 2004; 25:1109-1112. Temmerman OPP, Raijmakers PG, David EF, Pijpers R, Molenaar MA, Hoekstra OS, Berkhof J, Manoliu RA, Teule GJ, Heyligers IC. A comparison of radiographic and scintigraphic techniques to assess aseptic loosening of the acetabular component in a total hip replacement. J Bone Joint Surg Am 2004; 86:2456-2463.

Temmerman OPP, Heyligers IC, Teule GJ, Hoekstra OS, Raijmakers PG. The value of contrast and subtraction arthrography in the assessment of aseptic loosening of total hip prostheses: a meta-analysis. Eur J Radiol 2005; 56:113-119.

Temmerman OPP, Raijmakers PG, Hoekstra OS, Teule GJ, Berkhof J, Heyligers IC. Accuracy of diagnostic imaging techniques in the diagnosis of aseptic loosening of the femoral component of a hip prosthesis: a meta-analysis. J Bone Joint Surg Br 2005; 87(6):781-785. Termaat MF, Raijmakers PG, Scholten HJ, Bakker FC, Patka P, Haarman HJ. The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis: a systematic review and meta-analysis. J Bone Joint Surg Am 2005; 87:2464-2471. Van Tilburg EW, Franssen EJF, van der Hoeven JJM, van der Meij M, Elshove D, Lammertsma AA, Windhorst AD. Radiosynthesis of [11C]Docetaxel. J Label Compd Radiopharm 2004; 47:763-777.


Van Tinteren H, Hoekstra OS, Boers M. Do we need randomised trials to evaluate diagnostic procedures? Eur J Nucl Med Mol Imaging 2004; 31:129-131. Van Tinteren H, Smit EF, Hoekstra OS. FDG-PET in addition to conventional work-up in non-small-cell lung cancer. J Clin Oncol 2005; 23:1591-1592. Tony B, Vos MJ, Berkhof J, Postma TJ, van Lingen A, Heimans JJ, Hoekstra OS. Interobserver variability in the semi-quantitative assessment of 201Tl SPECT in cerebral gliomas. Nucl Med Commun 2005; 26:45-48. Torrenga H, Fabry H, van der Sijp J, van Diest PJ, Pijpers R, Meijer S. Omitting axillary lymph node dissection in sentinel node negative breast cancer patients is safe: a long term follow-up analysis. J Surg Oncol 2004; 88:4-7.

Veltman DJ, Tuinebreijer WE, Winkelman D, Lammertsma AA, Witter MP, Dolan RJ, Emmelkamp PM. Neurophysiological correlates of habituation during exposure in spider phobia. Psychiatry Res 2004; 132:149-158. Verel I, Visser GW, Vosjan MJ, Finn R, Boellaard R, van Dongen GA. High-quality 124I-labelled monoclonal antibodies for use as PET scouting agents prior to 131I-radioimmunotherapy. Eur J Nucl Med Mol Imaging 2004; 31:1645-52. Verel I, Visser GWM, van Dongen GAMS. The Promise of Immuno-PET in Radioimmunotherapy. J Nucl Med 2005; 46:164S-171S. Verheij J, van Lingen A, Raijmakers PG, Spijkstra JJ, Girbes AR, Jansen EK, van den Berg FG, Groeneveld AB. Pulmonary abnormalities after cardiac surgery are better explained by atelectasis than by increased permeability oedema. Acta Anaesthesiol Scand 2005; 49:1302-1310. Verheij J, Raijmakers PG, van Lingen A, Groeneveld AB. Simple vs complex radionuclide methods of assessing capillary protein permeability for diagnosing acute respiratory distress syndrome. J Crit Care 2005; 20:162-171. Vos MJ, Berkhof J, Postma TJ, Hoekstra OS, Barkhof F, Heimans JJ. Thallium-201 SPECT: the optimal prediction of response in glioma therapy. Eur J Nucl Med Mol Imaging 2006; 33:222-227.

Van der Weerdt AP, Boellaard R, Knaapen P, Visser CA, Lammertsma AA, Visser FC. Postinjection transmission scanning in myocardial 18F-FDG PET studies using both filtered backprojection and iterative reconstruction. J Nucl Med 2004; 45:169-75. Westerterp M, van Westreenen HL, Reitsma JB, Hoekstra OS, Stoker J, Fockens P, Jager PL, Eck-Smit BL, Plukker JT, van Lanschot JJ, Sloof GW. Esophageal cancer: CT, endoscopic US, and FDG PET for assessment of response to neoadjuvant therapy-systematic review. Radiology 2005; 236:841-851.

Van Westreenen HL, Westerterp M, Jager PL, van Dullemen HM, Sloof GW, Comans EFI, van Lanschot JJ, Wiggers T, Plukker JT. Synchronous Primary Neoplasms Detected on 18F-FDG PET in Staging of Patients with Esophageal Cancer. J Nucl Med 2005; 46:1321-1325.

Ten Wolde M, Hagen PJ, Macgillavry MR, Pollen IJ, Mairuhu AT, Koopman MM, Prins MH, Hoekstra OS, Brandjes DP, Postmus PE, Buller HR. Non-invasive diagnostic work-up of


patients with clinically suspected pulmonary embolism; results of a management study. J Thromb Haemost 2004; 2:1110-1117.

iii. International peer reviewed papers (external papers by members of staff)

Bart J, Dijkers ECF, Wegman TD, de Vries EGE, van der Graaf WTA, Groen HJM, Vaalburg W, Willemsen ATM, Hendrikse NH. New positron emission tomography tracer [11C]carvedilol reveals P-glycoprotein modulation kinetics. Br J Pharmacol 2005; 145:1045-1051.

Bokulic T, Vastenhouw B, de Jong HWAM, Van Dongen AJ, Van Rijk PP, Beekman FJ. Monte Carlo-based down-scatter correction of SPECT attenuation maps. Eur J Nucl Med Mol Imaging 2004; 31:1173-1181. Elsinga PH, Hendrikse NH, Bart J, van Waarde A, Vaalburg W. Positron emission tomography studies on binding of central nervous system drugs and P-glycoprotein function in the rodent brain. Mol Imaging Biol 2005; 7:37-44.

Hwang D, Narendran R, Huang Y, Slifstein M, Talbot P, Sudo Y, van Berckel BNM, Kegeles LS, Martinez D, Laruelle M. Quantitative analysis of N-[11C]propyl-norapomorphine ([11C]NPA) in vivo binding in nonhuman primates. J Nucl Med 2004; 45:338-346.

Kortekaas R, van Oostrom JCH, Willemsen ATM, Bart J, Leenders KL, Hendrikse NH. Blood-brain barrier dysfunction in Parkinsonian midbrain in vivo. Ann Neurol 2005; 57:176-179. Lavreysen H, Pereira SN, Leysen JE, Langlois X, Lesage AS. Metabotropic glutamate 1 receptor distribution and occupancy in the rat brain: a quantitative autoradiographic study using [3H]R214127. Neuropharmacology 2004; 46:609-619.

Lavreysen H, Willemoens T, Leysen JE, Lesage AS. Antagonist-induced supersensitivity of mGlu1 receptor signalling in cerebellar granule cells. Eur J Neurosci 2005; 21:1610-1616.

Leysen JE. 5-HT2 receptors. Curr Drug Targets CNS Neurol Disord 2004; 3:11-26.

Lubberink M, Kosugi T, Schneider H, Ohba H, Bergstrom M. Non-stationary convolution subtraction scatter correction with a dual-exponential scatter kernel for the Hamamatsu SHR-7700 animal PET scanner. Phys Med Biol 2004; 49:833-42.

Pindon A, Van Hecke G, Josson K, Leysen JE, Jurzak M. Internalization of human 5-HT4a and 5-HT4b receptors is splice variant dependent. Biosci Rep 2004; 24:215-223.

Razifar P, Lubberink M, Schneider H, Langström B, Bengtsson E, Bergström M. Non-isotropic noise correlation in PET data reconstructed by FBP but not by OSEM demonstrated using auto-correlation function. BMC Medical Imaging 2005; 5:3.

Sandström M, Tolmachev V, Kairemo K, Lundqvist H, Lubberink M. Performance of coincidence imaging with long-lived positron emitters as an alternative to dedicated PET and SPECT. Phys Med Biol 2004; 49:5419-5432.


Taymans JM, Kia HK, Claes R, Cruz C, Leysen J, Langlois X. Dopamine receptor-mediated regulation of RGS2 and RGS4 mRNA differentially depends on ascending dopamine projections and time. Eur J Neurosci 2004; 19:2249-2260. Taymans JM, Cruz C, Lesage A, Leysen JE, Langlois X. MK-801 alters RGS2 levels and adenylyl cyclase sensitivity in the rat striatum. Neuroreport 2005; 16:159-162. Taymans JM, Kia HK, Groenewegen HJ, Leysen JE, Langlois X. Bilateral control of brain activity by dopamine D1 receptors: evidence from induction patterns of regulator of G protein signaling 2 and c-fos mRNA in D1-challenged hemiparkinsonian rats. Neuroscience 2005; 134:643-656. Vaalburg W, Hendrikse NH, Elsinga PH, Bart J, van Waarde A. P-gp activity and biological response. Toxicol Appl Pharmacol 2005; 207:257-260. iv. National peer reviewed papers Becker A, van Agtmael MA, Comans EF, Voskuyl AE. Persistent fever in a patient with Salmonella typhimurium gonarthritis. Ned Tijdschr Geneeskd 2005; 149:33-36. Van Essenberg M, Luurtsema G, Lammertsma AA, Franssen EJF. Een spoortje radioactief water: de productie en klinische toepassingen van H2

15O-PET. Pharmaceutisch weekblad 2004; 12:400-405. Kuijpens JL, Verheij CD, Haak HR, Ribot JG, Hoekstra OS, Coebergh JW. Surgery and follow-up 131I therapy in patients with differentiated thyroid carcinoma in the south-east of the Netherlands, 1983-1996, compliance with the 1987 consensus guidelines. Ned Tijdschr Geneeskd 2004; 148:1835-1836. Visser OJ, Zijlstra JM, van Dongen GA, Huijgens PC. Radio-immunotherapy for B-cell non-Hodgkin lymphoma. Ned Tijdschr Geneeskd 2005; 149:2324-2328. Terwisscha van Scheltinga S, Meijer S, Cuesta MA, Pijpers R, Meijer GA, den Boer FC, van der Sijp JRM. Schildwachtklierprocedure bij colorectale carcinomen: huidige stand van zaken. Ned Tijdschr Oncol 2005; 2:43-48. Torrenga H,van Diest PJ, van der Wall E, Pijpers R, van der Sijp JRM, Meijer S. Gerandomiseerde studie ‘directe versus uitgestelde okselklierdissectie’ bij mammacarcinoom patiënten met een positieve schildwachtklier. Ned Tijdschr Oncol 2004; 1:185-189. v. Miscellaneous publications Van Essenberg M, Luurtsema G, Lammertsma AA, Franssen EJF. Een spoortje radioactief water: de productie en klinische toepassingen van [15O]H2O-PET. Tijdschr v Nucl Geneesk 2004; 26:46-49. Jager PL, Hoekstra OS. Richtlijnen voor NSCLC. Tijdschr v Nucl Geneesk 2005; 27:22-35.


Haslinghuis-Bajan LM, Hoekstra OS. Positron emissie tomografie in de oncologie. IKR bulletin zomer 2005. Greuter HNJM, Boellaard R, van Lingen A, Franssen EJF, Lammertsma AA. Measurement of [18F]FDG concentrations in blood samples: comparision of direct calibration and standard solution methods. Tijdschr v Nucl Geneesk 2005; 27:9-11. Greuter HNJM, van Ophemert PLB, Luurtsema G, Franssen EJF, Boellaard R, Lammertsma AA. Validation of a multiwell gamma-counter for measuring high pressure liquid chromatography metabolite profiles. Tijdschr v Nucl Geneesk 2005; 27:57-60. Regelink G, Pruim J, De Bree R, Van Der Laan BF, Hoekstra OS, Roodenburg JL. De rol van FDG PET voor de diagnostiek van patienten met een halskliermetastase van een onbekende primaire tumor. Ned Tijdschr v Oncol 2004; 1:49-53.

Hoekstra OS. De rol van positronemissietomografie in oncologie en hematologie. Oncollectie 2004; 2-8.

Lammertsma AA. Nieuwe PET-mogelijkheden voor in vivo onderzoek bij de ziekte van Alzheimer. Tijdschr v Nucl Geneesk 2004; 26:82-85. Termaat MF, Blokhuis TJ, Raijmakers PGHM, de Lange-de Klerk ESM, Bakker FC, Patka P, Haarman HJTM. Post-traumatic chronic osteomyelitis: a rare and problematic diagnosis? Osteosynthesis and Trauma Care 2005; 13:183-186. Termaat MF, Raijmakers PGHM, Bakker FC, Patka P, Haarman HJTM. The diagnostic value of FDG-PET in patients with suspected chronic bone infection. Osteosynthesis and Trauma Care 2005; 13:249-253. Termaat MF, Scholten HJ, Raijmakers PGHM, Bakker FC, Patka P, Haarman HJTM. Clinical cases of post-traumatic chronic osteomyelitis.A retrospective study. Osteosynthesis and Trauma Care 2005; 13:113-117. vi. Book chapters Manoliu RA, Hoekstra OS, Teule GJJ. Beeldvormende diagnostiek. In: Interne Geneeskunde. Ed. J van der Meer, 2005 (13e druk); uitg Bohn Stafleu van Loghem. Vansteenkiste J, Hoekstra OS, Stroobants S, Smit EF, Postmus PE. FDG PET in lung cancer. In: Lung Cancer: principles and practice; Eds. HI Pass, DP Carbone, DH Johnson, JD Minna. Philadelphia, Lippincott Williams & Wilkins (3rd edition), 2004 vii. Proceedings Boellaard R, Lubberink M, De Jong, H, Kropholler MA, Lammertsma AA. Application of various iterative reconstruction methods for quantitative 3D dynamic brain PET studies. In: 2004 IEEE Medical Imaging Conference Record. IEEE, Piscataway, New Jersey, USA, 2004: M2-217.


De Jong HWAM, Boellaard R, Michel C, Lammertsma AA. Quantitative accuracy of dynamic brain studies with the HRRT: a phantom study. In: 2004 IEEE Medical Imaging Conference Record. IEEE, Piscataway, New Jersey, USA, 2004: M9-403. De Jong HWAM, Knoess C, Lammertsma AA, Lenox M, Vollmar S, Casey M, Wienhard K, Heis W-D, Boellaard R. Performance characteristics of the high resolution research tomograph – comparison of three prototypes. In: 2004 IEEE Medical Imaging Conference Record. IEEE, Piscataway, New Jersey, USA, 2004: M9-107. De Jong HWAM, Perk L, Visser GWM, Boellaard R, van Dongen GAMS, Lammertsma AA. High Resolution PET imaging characteristics of 68Ga, 124I and 89Zr compared to 18F. In: 2005 IEEE Medical Imaging Conference Record. IEEE, Piscataway, New Jersey, USA, 2005: M03-160. Lammertsma AA. Role of human and animal PET studies in drug development. International Congress Series 2004; 1265: 3-11. Lubberink M, Schneider H, Lundqvist H - Modified dead time correction for prompt gamma radiation emitting PET isotopes. In: 2004 IEEE Medical Imaging Conference Record. IEEE: Piscataway, New Jersey, USA, 2004: M5-322. Sibomana M, Byars L, Panin V, Lenox M, Kehren F, Rist J, Burbar Z, Michel C, Knoess C, de Jong HWAM. Simultaneous measurement of transmission and emission contamination using a collimated 137Cs point source for the HRRT. In: 2004 IEEE Medical Imaging Conference Record. IEEE, Piscataway, New Jersey, USA, 2004: M2-317. Vesna Sossi, de Jong HWAM, Barker WC, Bloomfield P, Burbar Z, Camborde M-L, Comtat C, Eriksson LA, Houle S, Keator D, Knoß C, Krais R, Lammertsma AA, Rahmim A, Sibomana M, Teras M, Thompson CJ, Trebossen R, Votaw J, Walker M, Wienhard K, Wong DF. The Second Generation HRRT A Multi Centre Scanner Performance Investigation. In: 2005 IEEE Medical Imaging Conference Record. IEEE, Piscataway, New Jersey, USA, 2005: M07-269. Yaqub M, Boellaard R, Kropholler MA, Lubberink M, Lammertsma AA. Simulated annealing in pharmacokinetic modelling of PET neuroreceptor studies: accuracy and precision compared with other optimization algorithms. In: 2004 IEEE Medical Imaging Conference Record. IEEE, Piscataway, New Jersey, USA, 2004: M5-402. viii. Abstracts Van Balen SCM, Jongsma F, Schie van A, Comans EFI, Yaqub M, Lammertsma AA. A new protocol for diabetic patients for [F18]FDG whole body PET scans. Annual Congress European Association of Nuclear Medicine, Istanbul, Turkije, 2005. Eur J Nucl Med Mol Imaging 2005; 32 (suppl 1):S289. Van Berckel BNM, Boellaard R, Kropholler MA, Caspers E, Cahn W, Lammertsma AA, Kahn RS. Assessment of microglia activation in schizophrenia using [11C](R)-PK11195 and PET. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S391.


Boellaard R. Evaluation of basis function, linear and generalized linear least squares methods for generating cerebral blood flow and volume of distribution images. Neuroreceptor Mapping, Vancouver, Canada, 2004. Neuroimage 2004; 22 (suppl 2):T17-T18. Boellaard R, Kropholler MA, van Berckel BNM, Lammertsma AA. Generating parametric binding potential and volume of distribution images using a novel 2D basis function method and the two tissue compartment plasma input model. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S631. Boellaard R, Rijbroek A, Luurtsema G, Greuter H, Lammertsma AA. Feasibility of deriving CBF, OEF and CMRO2 from a single dynamic PET scan using a short inhalation of oxygen-15 labelled molecular oxygen. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S671. Boellaard R, van der Weerdt A, Visser FC, Lammertsma AA. Evaluatie van 2D- en 3D-cardiologische FDG-PET-studies m.b.v. een dynamisch scan protocol met afwisselende 2D- en 3D-acquisitieframes. Wetenschappelijke Vergadering NVNG, 2004. Tijdschr v Nucl Geneesk 2005; 27:19. Debets RMC, Comans EFI, Velis DN, Boas WV, Veltman DJ, Lammertsma AA. Indication for F-18-FDG or flumazenil PET in presurgical evaluation of patients with non-lesional temporal lobe epilepsy. Epilepsia 2004; 45 (suppl 3):181. Direcks WG, van Gelder M, Lammertsma AA, Molthoff CF. Imaging proliferation in breast cancer. Annual Congress Academy of Molecular Imaging, Orlando, USA, 2005. Mol Im Biol 2005; 7:129. Van Dongen GAMS, Borjesson PKE, Roos JC, Jauw YWS, Boellaard R, Comans EFI, Lammertsma AA, de Bree R, Leemans. Immuno-PET using zirconium-89-labeled chimeric MAb U36 for the detection of lymph node metastases in head and neck cancer patients. Annual Congress European Association of Nuclear Medicine, Istanbul, Turkey, 2005. Eur J Nucl Med Mol Imaging 2005; 32 (suppl 1):S79. Erritzoe D, Huang Y, Narendran R, van Berckel BNM, Hwang D, Bae SA, Laruelle M. PET comparison of the dopamine transsporter radioligands [11C]PE2I and [11C]altropane in non-human primates. Neuroreceptor Mapping, Vancouver, Canada, 2004. Neuroimage 2004; 22 (Suppl.2): T108. Geuze E, van Berckel BNM, Boellaard R, Windhorst AD, Luurtsema G, Westenberg HGM, Lammertsma AA, Vermetten E. Changes in benzodiazepine receptor binding in dutch veterans with posttraumatic stress disorder assessed with [C-11]-flumazenil and PET. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S619. Greuter HNJM, Takkenkamp K, Luurtsema G, Windhorst AD, Lammertsma AA. Optimizing an online SPE-HPLC method for analysis of [18F]N-(3-fluoropropyl)-2ß-carbomethoxy-3ß-(4-iodophenyl)nortropane ([18F]-FP-ß-CIT) and its metabolites in human plasma. In: Abstracts FIGON 7th Dutch Medicine Days, Lunteren, Netherlands, 2005: 29.


Hadithi M, Heine GDN, Comans EFI, Schie van A, Heijmans R, Blomberg von BME, Oudejans JJ, Hoekstra OS, Mulder CJ. Can PET Detect EATL/Lymphoma in Refractory Celiac Disease? 11th International Symposium on Coeliac Disease, Belfast, Northern Ireland, 2004. Hadithi M, Heine GDN, Comans EFI, Schie van A, Heijmans R, Blomberg, von BME., Oudejans JJ, Hoekstra OS, Mulder CJ. Can PET Detect EATL/Lymphoma in Refractory Celiac Disease? Digestive Disease Week, New Orleans, USA, 2004. Hendrikse NH. Visualization of physiological functions; Imaging of P-glycoprotein transport with positron emission tomography (PET). The first International Symposium on Resistant Cells “To die or not to die, is that resistant?”, Gwanju, South Korea, 2005. Herscheid JDM, Verbeek J, Booij J. Synthesis of 123I-radiopharmaceuticals with the label in a bridgehead position. 16th International Symposium on Radiopharmaceutical Chemistry, Iowa City, USA, 2005. J Label Compd Radiopharm 2005; 48 (suppl S1):S54. Herscheid JDM, Verbeek J, Booij, Braker AH. Bridgehead labelled WAY derivatives. A proof of concept towards metabolically inert radiopharmaceuticals. Meeting of the NWO Study Group Medicinal Chemistry in collaboration with the KNCV Section Medicinal Chemistry, Lunteren, Netherlands, 2005. De Jong HWAM, Boellaard R, van Berckel BNM, Ponsen MM, Lammertsma AA. Quantitative accuracy of the high resolution research tomograph: experimental and clinical evaluation. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S619. De Jong H, Boellaard R, Buijs, Lammertsma A. High resolution research tomograph: een PET-scanner voor dierstudies en humane hersenstudies. Wetenschappelijke Vergadering NVNG, 2004. Tijdschr Nucl Geneeskd 2005; 27:18-19. Joshi U, Raijmakers PGHM, van Lingen A, Comans EFI, Pijpers R, Teule GJJ, Hoekstra OS. Evaluation of pulmonary nodules: concordance of a prototype dual crystal (LSO/NaI) dual head coincidence camera and full ring positron emission tomography (PET). Annual Congress European Association of Nuclear Medicine, Helsinki, Finland, 2004. Eur J Nucl Med Mol Imaging 2004; 31:S293. Klumpers UMH, van Dyck R, Hoogendijk WJG, Veltman DJ, Lammertsma AA. [11C]flumazenil binding to GABA-A receptors in major depression decreases after therapy. Neuroreceptor Mapping, Vancouver, Canada, 2004. NeuroImage 2004; 22 (suppl 2):T45-T46. Klumpers UMH, Veltman DJ, Comans EFI, Kropholler MA, Boellaard R, Hoogendijk WJG, Lammertsma AA. Comparison of various models for analysing [11C]flumazenil studies. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S660.


Kropholler MA, Boellaard R, Schuitemaker A, van Berckel BNM, Lammertsma AA. Development of a plasma input model for analysis of [C-11](R)-PK11195 studies. Neuroreceptor Mapping, Vancouver, Canada, 2004. NeuroImage 2004; 22 (suppl 2):T184-T185. Kropholler MA, van Berckel BNM, Schuitemaker A, Folkersma H, Luurtsema G, Windhorst AD, Boellaard R, Lammertsma AA. Evaluation of reference tissue models for analysing [11C](R)-PK11195 studies. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands 2005. J Cereb Blood Flow Metab 2005; 25:S642. Van der Laken CJ, Molthoff CFM, Lammertsma AA, Dijkmans BAC, Voskuyl AE. Visualization of macrophages in rheumatoid synovitis by positron emission tomography and autoradiography. Eular Conference, Berlin, Germany, 2004. Ann Rheum Dis 2004; 63 (suppl 1):83. Van der Laken CJ, Molthoff CFM, Lammertsma AA, Dijkmans BAC, Voskuyl AE. Visualization of macrophages in rheumatoid synovitis by positron emission tomography and autoradiography. American College of Rheumatology, San Antonio, USA, 2004. Arthritis Rheum 2004; 50 (suppl):S173. Lammertsma AA. Dedicated brain scanners – opportunities and pitfalls. In: Abstract Book “X Turku PET Symposium”, Turku, Finland, 2005: 16. Liefaard LC, Ploeger BA, Molthoff CFM, Boellaard R, de Jong HWAM, Lammertsma AA, Danhof M,Voskuyl RA. Development of longitudinal PET studies for experimental animal models. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S602. Lubberink M, Boellaard R, Greuter HNJM, Lammertsma AA. Effect of uncertainty in plasma metabolite levels on kinetic analysis of [11C]flumazenil and [11C]PK-11195 PET studies. Neuroreceptor Mapping, Vancouver, Canada, 2004. Neuroimage 2004; 22 (suppl 2):T119-120. Lubberink M, Boellaard R, van der Weerdt AW, Visser FC, Lammertsma AA. Quantitative evaluation of OSEM and FBP reconstructions for dynamic 2D and 3D cardiac FDG PET studies. Annual Congress Academy of Molecular Imaging, Orlando, USA, 2004. Mol Imag Biol 2004; 6:99. Lubberink M, Joshi U, De Jong HWAM, Teule GJJ, Hoekstra OS, Van Lingen A. Comparison of lesion detectability of six different pet scanners: an observer study of thorax phantom images. Annual Meeting Society of Nuclear Medicine, Toronto, Canada, 2005. J Nucl Med 2005; 46. Lubberink M, Luurtsema G, Van Berckel BNM, Boellaard R, Toornvliet R, Franssen EJF, Lammertsma AA. Development of a tracer kinetic model for the analysis of (R)-[11C]verapamil PET data. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S608. Lubberink M, Luurtsema G Boellaard R, Lammertsma AA. Multi-input spectral analysis for evaluation of the contribution of radioactive metabolites in (R)-[11C]verapamil PET data.


International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S629. Lubberink M, Schie van A, de Jong HWAM, Dongen van GAMS, Teule GJJ. Acquisition settings for PET imaging of 124I simultaneously administered with therapeutic amounts of 131I. Annual Meeting Society of Nuclear Medicine, Toronto, Canada, 2005. J Nucl Med 2005; 46 (suppl). Luurtsema G, Schuit RC, Greuter HNJM, Takkenlamp K, Windhorst AD, Franssen EJF, van Berckel BNM, Lubberink M, van Ophemert PLB, Toornvliet R, Lammertsma AA. Metabolic profile of (R)-[11C]verapamilin human plasma. 16th International Symposium on Radiopharmaceutical Chemistry, Iowa City, USA, 2005. J Label Compd Radiopharm 2005; 48 (suppl S1):S341. Luurtsema G, Schuit RC, Greuter HNJM, Takkenlamp K, Windhorst AD, Franssen EJF, van Berckel BNM, Lubberink M, van Ophemert PLB, Toornvliet R, Lammertsma AA. Metabolic profile of (R)-[11C][11C]verapamilin human plasma. In: Abstracts FIGON 7th Dutch Medicine Days, Lunteren, Netherlands, 2005: 55. Mesina CT, Jongbloed G, Boellaard R, van der Vaart AW, Lammertsma AA. Comparison of various methods for detecting activation using PET. Human Brain Mapping, Budapest, Hungary, 2004. NeuroImage 2004 (suppl):WE370. Van der Mey M, Windhorst AD, Kennis L, Bisshof F, Klok RP, Bakker M, Langlois X, Heylen L, Herscheid JDM, Jurzak M, Leysen JE. Synthesis and in vivo studies of [11C]R107474, a new radiolabeled α2-adrenoceptor antagonist. In: Abstracts FIGON 7th Dutch Medicine Days, Lunteren, Netherlands, 2005: 32. Rajasekharan S, Boellaard R, Lubberink M, Lammertsma AA, Jones T. Measurement of abdominal tumour blood flow: independent assessment of delay and dispersion of the arterial input function. IEEE Medical Imaging Conference, Rome, Italy, 2004. Van Rij CM, Huitema ADR, Swart EL, Greuter HNJM, Lammertsma AA, van Loenen AC, Franssen EJF. Populatie farmacokinetiek van tracer doseringen 11C-flumazenil bij positron emissie tomografie. Wetenschappelijke Vergadering NVNG, 2004. Tijdschr v Nucl Geneesk 2005; 27:15. Van Rij CM, Swart EL, Greuter HNJM, van Loenen AC, Lammertsma AA, Franssen EJF. Population plasma pharmacokinetics of tracer quantities of 11C-flumazenil. Br J Clin Pharmacol 2004; 58:111. Schie van A, Raijmakers PGHM, Waesberghe van JHTM, Hoekstra OS. De vergrote bijnier en het primair bronchuscarcinoom: epidemiologische aspecten en de waarde van PET en CTin de differentiatie tussen benigniteit en maligniteit. Wetenschappelijke Vergadering NVNG, Arnhem, Netherlands, 2004. Tijdschr v Nucl Geneesk 2005; 27:19. Schuitemaker A, van Berckel BNM, Boellaard R, Kropholler MA, Jonker C, Veltman DJ, Scheltens P, Lammertsma AA. Assessment of microglial activation in patients with Alzheimer’s disease using [C-11]-(R)-PK11195 and PET. International Symposium on Cerebral Blood Flow,


Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S318. Schuitemaker A, van Berckel BNM, Boellaard R, Kropholler MA, Jonker C, Veltman DJ, Scheltens P, Lammertsma AA. Imaging of microglial activation in patients with Alzheimer’s disease using [C-11](R)-PK11195 PET. European Neuropsychopharmacology Congress, Amsterdam, Netherlands, 2005. Eur Neuropsychopharmacol 2005; 15: S571. Schuitemaker A, van Berckel BNM, Kropholler M, Boellaard R, Jonker C, Scheltens P, Lammertsma AA. Microglia activation in mild cognitive impairment. 9th International Conference on Alzheimer’s Disease and Related Disorders. Neurobiology of aging 2005; 25 (suppl S2):286. Schuitemaker A, van Berckel BNM, Kropholler MA, Scheltens P, Jonker C, Veltman DJ, Lammertsma AA, Boellaard R. Effects of reference tissue versus plasma input parametric kinetic modelling on statistical parametric analysis of [11C](R)-PK11195 binding in Alzheimer’s disease (AD) and young and old subjects. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S643. Schuitemaker A, Kropholler MA, Boellaard R, van Berckel BNM, Jonker C, Scheltens Ph, Lammertsma AA. (R)-[11C]-PK11195 studies in patients with Mild Cognitive Impairment. Neuroreceptor Mapping, Vancouver, Canada, 2004. NeuroImage 2004; 22 (suppl 2):T91-T92. Schuitemaker A, Mulder C, Schoonenboom NS, Ketema M, van Elk EJ, Scheltens P, van Kamp GJ. Inflammatory markers CRP and IL-6 in cerebrospinal fluid and serum in relation to the IL-6 genotype in patients with Alzheimer's disease. 9th International Conference on Alzheimer’s Disease and Related Disorders. Neurobiology of aging 2005; 25 (suppl S2):363-364. Termaat MF, Raijmakers PGHM, Scholten HJ, Patka P, Bakker FC, Haarman HJTM. The accuracy of diagnostic imaging for the assessment of chronic osteomyelitis; Systematic review and meta-analysis. Annual Congress European Association of Nuclear Medicine, Helsinki, Finland, 2004. Eur J Nucl Med Mol Imaging 2004; 31:S276-S277. Tilburg EW van, van der Mey M, Windhorst AD, Herscheid JDM. One-pot synthesis of [11C]ureas via triphenylphosphinimines. 16th International Symposium on Radiopharmaceutical Chemistry, Iowa City, USA, 2005. J Label Compd Radiopharm 2005; 48 (suppl S1):S133. Toornvliet JR, Van Berckel BNM, Luurtsema G, Lubberink M, Geldof AA, Bosch TM, Lammertsma AA, Franssen EJF. Effect of age on P-glycoprotein blood brain barrier transport function studied with (R)-[11C]verapamil and PET. Meeting Dutch Society of Clinical Pharmacology and Biopharmacy, 2005. Br J Clin Pharmacol 2005; 60:679. Toornvliet JR, van Berckel BNM, Luurtsema G, Lubberink M, Geldof AA, Bosch TM, Lammertsma AA, Franssen EJF. Effect of age on blood brain barrier transport function studied with [11C](R)-verapamil and PET. FIGON 7th Dutch Medicine Days, Lunteren, Netherlands, 2005. Toornvliet JR, Van Berckel BNM, Luurtsema G, Lubberink M, Geldof AA, Bosch TM, Lammertsma AA, Franssen EJF. Effect of age on blood brain barrier transport studied with (R)-[11C]verapamil and PET. International Symposium on Cerebral Blood Flow, Metabolism,


and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S273. Van der Veldt AA, Hooft L, van Diest PJ, Buist MR, Comans EF, Lammertsma AA, Hoekstra OS, Molthoff CF. CD31 and P53 profiles in selecting cervical cancer patients for positron emission tomography in early detection of recurrence. Annual Congress Academy of Molecular Imaging, Orlando, USA, 2005. Mol Im Biol 2005; 7:115. Verheij J, Groeneveld AB, Beishuizen A, van Lingen A, Simoons-Smit AM, van Schijndel RJ. Herpes simplex virus type 1 and normal protein permeability in the lungs of critically ill patients: a case for low pathogenicity? Crit Care 2004; 8:R139. Westerterp M, Pruim J, Oyen WJ, Hoekstra OS, Paans A, Visser E, Sloof G, Boellaard R. Quantification of FDG PET studies using standardized uptake values in multi-center trials; effects of acquisition, image reconstruction and ROI definition parameters. Annual Meeting Society of Nuclear Medicine, Toronto, Canada, 2005; 46 (suppl). Wolfensberger SPA, Airaksinen AJ, van Berckel BNM, Boellaard R, Carey WDH, Reddingius W, Veltman DJ, Windhorst AD, Leysen JE, Lammertsma AA. Evaluation of [11C]R116301 as a tracer for the in vivo measurement of NK1 receptors in human subjects. In: Abstracts FIGON 7th Dutch Medicine Days, Lunteren, Netherlands, 2005: 31. Wolfensberger SPA, Araiksinen AJ, van Berckel BNM, Boellaard R, Carey WDH, Reddingius W, Veltman DJ, Windhorst AD, Leysen JE, Lammertsma AA. Evaluation of [C-11]R116301 as a tracer for the in vivo measurement of NK-1 receptors in human subjects. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S596. Wolfensberger SPA, van Berckel BNM, Araiksinen AJ, Boellaard R, Carey WDH, Reddingius W, Veltman DJ, Windhorst BD, Leysen JE, Lammertsma AA. Evaluation of [11C]R116301 as a potential PET ligand for investigating NK1 receptors in human subjects. European Neuropsychopharmacology Congress, Amsterdam, Netherlands, 2005. Eur Neuropsychopharmacol 2005; 15:S645-S646. Yaqub M, Boellaard R, Kropholler M, Lubberink M, Lammertsma AA. Improving accuracy and precision of PET pharmacokinetic analysis using wavelet based denoising of time activity curves. International Symposium on Cerebral Blood Flow, Metabolism, and Function & International Conference on Quantification of Brain Function with PET, Amsterdam, Netherlands, 2005. J Cereb Blood Flow Metab 2005; 25:S640.