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.