Preclinical Studies of Modern Radiopharmaceuticals: Expert Approaches to Evaluating the Results

INTRODUCTION. Development of safe and efficacious radiopharmaceutical medicines (radiopharmaceuticals) requires a legally, organisationally and scientifically sound regulatory system. Due to the lack of current Russian and Eurasian Economic Union (EAEU) guidelines for preclinical development of radiopharmaceuticals, international approaches to the scope of preclinical research and expert review of the obtained results.
AIM. The study aimed to update expert approaches to preclinical studies of modern radiopharmaceuticals by analysing the relevant scientific recommendations, current regulatory requirements, and expertise in Russia and abroad.
DISCUSSION. In general, radiopharmaceuticals are considered as medicinal products in most countries. To introduce an originator product on the market, a full development cycle is required, including assessment of specific activity, toxic properties, pharmacokinetic and pharmacodynamic parameters. General principles of preclinical studies set out in the relevant EAEU guidelines are applicable to research of radiopharmaceuticals, with radioactivity being a special property that requires consideration. Specific preclinical studies of targeted radiopharmaceuticals include: defining pharmacological target; selecting and developing targeting vectors for radionuclide delivery; selecting chelators for coupling radionuclides to vectors; choosing a radionuclide; assessing in vitro binding specificity and activity; assessing cytotoxicity; selecting a relevant in vivo model for assessing biodistribution and therapeutic efficacy or imaging; dosimetry; toxicological studies; and preparing for translation into clinical trials. General form of the European Union’s non-clinical assessment report of preclinical mostly coincides with the EAEU expert report on preclinical (non-clinical) study results.
CONCLUSIONS. The approach to conducting preclinical studies of radiopharmaceuticals and assessing their results is fundamentally similar in the EAEU and the European Union. Basic regulatory and expert requirements can be defined, alongside with the general recommendations for preclinical development of radiopharmaceuticals. Together with common methodological recommendations, it is reasonable to compile appendices for certain radiopharmaceutical groups based on current scientific data and regulatory experience in the Russian Federation and abroad.

1. Klementyeva OE, Smirnova AV, Kulbachevskaya NYu, et al. Non-clinical studies of radiopharmaceuticals: analysis of national and international regulatory practice (Review). Regulatory Research and Medicine Evaluation. 2024;14(3):251–64 (In Russ.). https://doi.org/10.30895/1991-2919-2024-14-3-251-264

2. Vorontsova MS, Karmakova TA, Pankratov AA, Kaprin AD. Current trends in targeted radionuclide therapy development. Medical Radiology and Radiation Safety. 2021;66(6):63–70 (In Russ.). https://doi.org/10.12737/1024-6177-2021-66-6-63-70

3. Zyryanov SK, Zatolochina KE. Perspective for use of the radionuclide drugs in the treatment of malignant tumors in Russia. Good Clinical Practice. 2018;(2):51–7 (In Russ.). https://doi.org/10.24411/2588-0519-2018-10044

4. Bezborodova OA, Pankratov AA, Nemtsova ER, et al. Anti-tumour drugs: Planning preclinical efficacy and safety studies. Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2020;10(2):96–110 (In Russ.). https://doi.org/10.30895/1991-2919-2020-10-2-96-110

5. Kovalchuk MV, Deev SM, Sergunova KA. Targeted nuclear medicine. Achievements, problems and prospects. Russian Nanotechnologies. 2023;18(4):436–55 (In Russ.). https://doi.org/10.56304/S1992722323040088

6. Lunev AS, Petrosova KA, Ternovskaya KE, et al. Analysis of current rules and regulations for preclinical studies of radiopharmaceuticals. Regulatory Research and Medicine Evaluation. 2024;14(1):81–90 (In Russ.). https://doi.org/10.30895/1991-2919-2024-14-1-81-90

7. Zavaleva EV, Zavalev VI, Andruzskaya AG, Zyabkin IV. Issues of regulatory regulation of preclinical (non-clinical) studies: Achievments, problems and prospects. Kremlin Medicine Journal. 2024;(3):90– 5 (In Russ.). https://doi.org/10.48612/cgma/23m1-3xax-nahf

8. Ponomareva D.V. Legal regime for circulation of high-tech medicinal products: Experience of interstate integration associations. Lex Genetica. 2025;4(2):28–46 (In Russ.). https://doi.org/10.17803/lexgen-2025-4-2-28-46

9. Korde A, Mikolajczak R, Kolenc P, et al. Practical considerations for navigating the regulatory landscape of non-clinical studies for clinical translation of radiopharmaceuticals. EJNMMI Radiopharm Chem. 2022;7(1):18. https://doi.org/10.1186/s41181-022-00168-x

10. Filosofov DV, Baimukhanova AE, Kurakina ES , et al. Radiochemistry for radiopharmaceutical nuclear medicine at the Laboratory of nuclear problems of JINR. Physics of Elementary Particles and Atomic Nuclei. 2023;54(4):377–450 (In Russ.). EDN: YITIYA

11. Nelson BJB, Krol V, Bansal A, et al. Aspects and prospects of preclinical theranostic radiopharmaceutical development. Theranostics. 2024;14(17):6446–70. https://doi.org/10.7150/thno.100339

12. Kosenko VV, Trapkova AA, Kalmykov SN. Regulation of radiopharmaceutical products. Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. Regulatory Research and Medicine Evaluation. 2022;12(4):379–88 (In Russ.). https://doi.org/10.30895/1991-2919-2022-12-4-379-388

13. Kodina GE, Malysheva AO. The main issues of quality assurance of radiopharmaceuticals. Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2019;9(4):216–30 (In Russ.). https://doi.org/10.30895/1991-2919-2019-9-4-216-230

14. Schwarz SW, Decristoforo C, Goodbody AE, et al. Harmonization of United States, European Union and Canadian first-in-human regulatory requirements for radiopharmaceuticals — is this possible? J Nucl Med. 2018;jnumed.118.209460. https://doi.org/.2967/jnumed.118.209460

15. Schwarz SW, Decristoforo C. US and EU radiopharmaceutical diagnostic and therapeutic nonclinical study requirements for clinical trials authorizations and marketing authorizations. EJNMMI Radiopharm Chem. 2019;4(1):10. https://doi.org/10.1186/s41181-019-0059-2

16. Perera M, Morris MJ. From concept to regulatory drug approval: Lessons for theranostics. J Nucl Med. 2022;63(12):1793–801. https://doi.org/10.2967/jnumed.121.263301

17. Korde A, Mikolajczak R, Kolenc P, et al. Practical considerations for navigating the regulatory landscape of non-clinical studies for clinical translation of radiopharmaceuticals. EJNMMI Radiopharm Chem. 2022;7(1):18. https://doi.org/10.1186/s41181-022-00168-x

18. Decristoforo C, Neels O, Patt M. Emerging radionuclides in a regulatory framework for medicinal products — How do they Fit? Front Med (Lausanne). 2021;8:678452. https://doi.org/10.3389/fmed.2021.678452

19. Nelson BJB, Krol V, Bansal A, et al. Aspects and prospects of preclinical theranostic radiopharmaceutical development. Theranostics. 2024;14(17):6446–70. https://doi.org/10.7150/thno.100339

20. Zhang S, Wang X, Gao X, et al. Radiopharmaceuticals and their applications in medicine. Signal Transduct Target Ther. 2025;10(1):1. https://doi.org/10.1038/s41392-024-02041-6

21. Antonyuk AV, Kozhukhar YuV, Ivanova TM, Sinolits AV. Review and prospects of use in Russia of 131I-MIBG (Azedra) and 177Lu-dotatate (Lutatera) drugs and their diagnostic pairs for visualization and therapy of neuroendocrine tumors. In: Collection of abstracts of the II All­Russian Congress with international participation “NUCLEAR MEDICINE — 2023”. St. Petersburg: Granov RRCRST; 2023. P. 19–20 (In Russ.).

22. Goryachev DV, Lysikova IV, Chernaya AA, Beshlieva ED. Developing marketing authorisation dossier of a radiopharmaceutical: the EAEU procedure. Regulatory Research and Medicine Evaluation. 2025;15(4):451–60 (In Russ.). https://doi.org/10.30895/1991-2919-2025-15-4-451-460

23. Goryachev DV, Lysikova IV, Chernaia AA, Kushnir DD. Planning a clinical development programme for radiopharmaceuticals: An analysis of international guidelines and expertise. Regulatory Research and Medicine Evaluation. 2025;15(1):105–20 (In Russ.). https://doi.org/10.30895/1991-2919-2025-15-1-105-120