Interdisciplinary consortium collaboration for the development of

radiopharmaceutical approach for effective

diagnostics and therapy of prostate cancer in Russia

K. German1,2, O. Vlasova3, V. Petriev4, V. Skvortsov4, G.Kodina5, A. Maruk5, N. Airapetova6, N. Epshtein6, N. Nerozin3,A. Safonov1,2, V. Lebedev1, Ya. Obruchnikova1,2, Yu. Shevko3

1 - A.N. Frumkin Institute of Physical Chemistry and Electrochemistry RAS, Moscow

2 - Medical Institute Reaviz, Moscow branch, Russia

3 - A. I. Leipunsky Institute for Physics and Power Engineering, Obninsk, Russia

4 - Medical Radiological Research Center of Ministry of Health of Russia, Obninsk, Russia

5 - Burnazyan Federal Medical Biological Center of FMBA, Moscow, Russia

6 - National Research Nuclear University MEPhI, Obninsk, Russia

Consortium organigram

Direсtorate

A.N. Frumkin Institute of Physical

Chemistry and Electrochemistry RAS,

Moscow

Medical Institute Reaviz, Moscow branch,

Russia

Burnazyan Federal Medical Biological Center of FMBA, Moscow, Russia

National Research Nuclear University MEPhI, Obninsk,

Russia

Medical Radiological Research Center of

Ministry of Health of Russia, Obninsk, Russia

A. I. Leipunsky Institute for Physics and Power

Engineering, Obninsk, Russia

Tc-99m for prostate cancerdiagnostics and

Re-188 for treatment

A.N. Frumkin Institute of Physical Chemistry and Electrochemistry RAS,

MoscowTechnetium chemistry laboratory

• K. German, Project CEO, Head of Tc laboratory, PhD , Doc., Prof.

• A. Safonov, Deputy head of Tc laboratory, PhD

• Ya. Obruchnikova, PhD

• V. Tregubova, PhD student

• M. Glazkova

Innovation department

• V. Lebedev, General manager for innovations

Laboratory of new physical-chemical problems

• A. Tsivadze, Director of IPCE RAS, Academician

• A. Filyanin, liquid extraction group, PhD

• V. Tarasov, NMR analysis, Professor

Laboratory of substance radiation chemistry

• B. Ershov, Head of laboratory, corr. member RAS, Professor

• E. Abkhalimov, PhD

• R. Solovov, PhD student

Laboratory of interphase boundaries and electocatalysis

• V. Andreev, Head of laboratory, Professor

Laboratory of radioactive material analysis

• M. Grigoriev, Head of laboratory, Professor

• The main purpose of the Institute is to carry out fundamental and applied scientific research in various fields of physical chemistry, electrochemistry, chemical resistance of materials, radiochemistry and radiation chemistry.

A. I. Leipunsky Institute for Physics and Power Engineering, Obninsk, Russia

• O. Vlasova, N. Nerozin, Yu. Shevko, I. Zhuk

• multidisciplinary scientific organization, conducting complex investigations of physical and technical problems of nuclear science and technology.

Medical Radiological Research Center of Ministry of Health of Russia,

Obninsk, Russia

• V. Skvortsov, V. Petriev• Mission: Development of concepts, regulatory

documents related to radiation safety of a human and the environment, health security and reduction of socioeconomic prejudice caused by radiation.

• The Institute was founded in 1962 to develop and improve methods of radiation diagnostics and radiation therapy, prevention and treatment of radiation injury, the study of the biological and medical effects of ionizing radiation.

National Research Nuclear University MEPhI, Obninsk, Russia

• N. Airapetova, N. Epshtein

• Development of analytical procedures for quality control of radiopharmaceuticals and staff training

• Mission: to generate, disseminate the use and to preserve scientific knowledge aiming to address global challenges of the XXI century, as well as to provide innovative transformations in Russia accompanying development of the country competitiveness in the global energy and non-energy high-tech markets.

Burnazyan Federal Medical Biological Center of FMBA, Moscow, Russia

• G. Kodina, PhD, Department head• A. Maruk, PhD, Laboratory Head• Production of Tc-99m (for radiodiagnostics)

and Re-188 (for radiotherapy) isotopes and preclinical medicine tests

• Fundamental and applied research in the field of radiation medicine, radiobiology and radiation protection; • Research in the field of biomedical technologies, radiopharmacy;• Development of new radiation technologies (including photon and neutron capture therapy); • Research in the field of chemical and radiation safety in the use of technology for special applications.

Medical Institute Reaviz, Moscow branch, Russia

• K. German, Chair of Natural science, Professor

• A. Safonov, docent, PhD

• Ya. Obruchnikova, assistant prof., PhD

• V. Tregubova, PhD student

• Training of medical staff for modern medicine

“The main aim of Reaviz is the training of health care staff, of young people who should become highly professional physicians in the nearest future. The most important quality for these professionals should be the integration of the greatest responsibility and the inner freedom of this profession, of scientific research and practical achievements.” Rector of Samara Medical Institute “REAVIZ”, Doctor of Medical Science, professor Nikolay A. Lyssov

What we intend to obtain

In the course of this project should be developed

• production technologies of 99mTc generators and high-value 188Re generators with reduced transport index,

• technologies of 188Re concentration, development of analytical methods for detection of radioactive and chemical impurities in the 188Re preparation,

• quality assurance of 99mTc and 188Re generator eluatesin accordance with the requirements of potential radiopharmaceuticals based on them, specifically binds to the receptor tissue of prostate cancer.

What we already have for radionuclide imaging

• 2-18F-fluoro-2-deoxy-D-glucose (FDG);• 111In-7E11 antibody (ProstaScint);• 18F-fluorodihydrotestosterone (18F-FDHT); • radioacetate analogs; • radiocholine analogs; • anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic

acid (anti-[18F]FACBC)Production of Tc-99m (for radiodiagnostics) and Re-188 (for radiotherapy) isotopes were improved with optimized generator design aimed to high specific activity production.

• Potential consumer of radiopharmaceuticals (RPh): medical institutions at various levels, cancer medical centers, cancer clinics, licensed to work with sources of ionizing radiation and equipped with diagnostic equipment, SPECT or PET.

• Objects of RPh application: patients with the disease of prostate cancer (about 30 thousand pers. / year).

• Over the past few years in Russia approximately 40,000 new cases of prostate cancer per year were recorded, and only for 30% of them brachytherapy is performed with an efficiency of 75%

Effective diagnostics and therapy of prostate cancer is an important issue

for Russia due to constantly increasing number of decease cases herein.

Rational development of new radiopharmaceuticals for the management of advanced and metastatic prostate cancer requires an improved cooperation of the organization thus involved. For this reason an interdisciplinary consortium collaboration for the development of radiopharmaceutical approach is established with principle aim to improve the situation within the 3 coming years.

The development of new radiopharmaceuticals and generators for the management of advanced prostate cancer will help to improve the treatment of this disease in Russia.

• Special educational interdisciplinary program for specialist training for technetium application to prostate radiodiagnostics is elaborated.

• The development of new radiopharmaceuticals and generators for the management of advanced prostate cancer will help to improve the treatment of this disease in Russia.

• Innovative character of this project requires special attention on staff training.

• New technologies worked out by Igor Zhuk and Yury Shevko (A.I. Leipunsky Institute for Physics and Power Engineering, Obninsk, Russian Federation) are to be used in this project

A new approach to

form a competent team of

specialists

What makes a good specialist?

Objectivity Creativity

Interest Competence

Self-criticism

Efficiency

Many issues written by leading scientists state that the expert is endowed mainly the

following qualities, namely:

1) has a degree in the subject area;2) has a positive experience with previous expertise in the subject area;3) must work at least 10 years;4) objective;5) must constantly improve their knowledge and so on.

Is it true?

In our opinion, these qualities are of a formalnature and do not meet the full competenciesthat have been proposed by the Europeancommunity as one of the core competences forprofessionals of the twenty-first century.

Five basic EU competencies were chosen as the most necessary for the Expert of the XXI century :

1. Communication in the mother tongue.2. Communication in foreign languages.3. Mathematics skills and core competencies

(skills) in science and technology.4. Information technology competence.5. The ability to find new information and

produce new knowledge for expert’s

professional area.

Ask yourself: “Are you sure that You have all this basic competencies?”

Or Do You think that the expert and specialist of technetium application to prostate

radiodiagnostics do not need this competencies?

Unfortunately, it is not a simple question.

Please, think about quantity of the wrong diagnosis in different countries

Thank you for the attention !

• The PSMA markers are focus selection of the project due to their ability not only for cancer but also for methastatic object detection. Draw investigation indicated that the prostate-specific membrane antigen (PSMA) based markers could be the key substrate matter for the solution of the problem. PSMA is highly expressed in prostate cancer, and small-molecule radiopharma-ceuticals targeting PSMA helps to rapidly detect the location and extent of disease. Comparative study provided with a selected row of substrates including several MIP derivatives and some others. Synthetic procedures were optimized for better yields, purities and prices.

Expert assessments in Russia

• Expert assessments are applied with success in various fields of human activity and find their reflection in the works of such Russian scientists as Azgaldov G.G., Beshelev S.D., Evlanov L.G., Gurvich F.G., Larichev O.I., LitvakB.G., Novikov, D. A., Orlov, A.I., Raichman I.P., Sidelnikov Y.V., and many other authors involved in problem of expert assessments.

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Evlanov L.G. thought that the expert has the following requirements:

1) Competence;2) Creativity;3) Respect to the examination;4) Conformism;5) Constructive thinking;6) Teamwork;7) Self-criticism.

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In the work of Raichman A.P. and Azgldov G.G. the quality of the expert has the following requirements:

1) Competence;2) Interest;3) Efficiency;4) Objectivity.The competence of the expert should be applied to the object quality assessment (professional competence) and methodology (qualitative competence).

Data about the authors

• Zhuk Igor Aleksandrovich, PHD,

• Shevko Yuri Viktorovich, e-mail: zz-38@yandex.ru

• (A. I. Leipunsky Institute for Physics and Power Engineering, Obninsk, Russia)