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 organigramDireсtorate

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

• 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

Роль института в проекте

• Кто входит в проект

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

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

Medical Radiological Research Center of Ministry of Health of Russia,

Obninsk, Russia

• V. Skvortsov, V. Petriev

National Research Nuclear University MEPhI, Obninsk, Russia

• N. Airapetova, N. Epshtein• Development of analytical procedures for

quality control of radiopharmaceuticals and staff training

Burnazyan Federal Medical Biological Center of FMBA, Moscow, Russia

• G. Kodina, A. Maruk• Production of Tc-99m (for radiodiagnostics)

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

Medical Institute Reaviz, Moscow branch, Russia

• K. German, Chair of Natural science, Professor • A. Safonov, docent, PhD• Ya. Obruchnikova, PhD• V. Tregubova, PhD student

• Training of medical staff for modern medicine

What we intend to obtain

• В ходе выполнения ПНИЭР должны быть разработаны технологии производства генераторов 99mТс и 188Re генераторов большого номинала со сниженным транспортным индексом, технологии концентрирования 188Re, разработка аналитических методик определения радиоактивных и химических примесей в препарате 188Re, обеспечение качества элюатов из генераторов 99mТс и 188Re в соответствии с требованиями потенциальных радиофармпрепаратов на их основе, специфически связывающихся с рецепторами тканей рака предстательной железы.

• Потенциальный потребитель РФП – медицинские учреждения различных уровней, онкологические медицинские центры, онкологические диспансеры, лицензированные для работы с источниками ионизирующего излучения и оснащенные диагностическим оборудованием ОФЭКТ или ПЭТ.

• Объекты применения РФП – пациенты с заболеванием РПЖ (порядка 30 тыс. чел./год).

• За последние несколько лет в РФ регистрировалось примерно 40 000 первичных случаев рака предстательной железы в год, из которых, по медицинским показаниям, только в 30% случаев проводится брахитерапия с эффективностью 75%.

• brachytherapy

• На сегодняшний день, существующими и разрабатываемыми агентами (биомаркерами) для радионуклидной визуализации РПЖ, которые проходят клинические исследования, являются:

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

(anti-[18F]FACBC).

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 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.

• Production of Tc-99m (for radiodiagnostics) and Re-188 (for radiotherapy) isotopes were improved with optimized generator design aimed to high specific activity production.

• 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, Yury Shevko(A.I. Leipunsky Institute for Physics and Power Engineering, Obninsk, Russian Federation) are to be used in this project

• 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.

A new approach to form a competent team of specialist

THE BASIC COMPETENCE OF THE EXPERT AND SPECIALIST TRAINING FOR TECHNETIUM APPLICATION TO PROSTATE

RADIODIAGNOSTICS.

What makes a good specialist?

Objectivity Creativity

Interest Competence

Self-criticism

Efficiency

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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., Litvak B.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.

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).

Many books are written by leading scientists, where 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 formal nature and do not meet the full competencies that have been proposed by the European community as one of the core competences for professionals of the twenty-first century.

The authors choose five Basic EU competencies for the Expert of the twenty-first 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 simple question. Please, think about quantity of the wrong

diagnosis in different countries

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)

Thank you for the attention !