A.E. Krasheninnikov, Cand. farm. Sci., General Director of ANO “National Scientific pharmacovigilance center “, Moscow, anatoly.krasheninnikov@drugsafety.ru

A. V. Matveev, Ph.D. honey. Sciences, Associate Professor of the Department of Internal Medicine No. 1 with a course of clinical Pharmacology Medical Academy. S. I. Georgievsky Federal State Autonomous Educational Institution of Higher Education “Crimean Federal University named after V. I. Vernadsky “, Simferopol, executive director of ANO” National National Scientific Center for Pharmacovigilance “, Moscow, avmcsmu@gmail.com

E. A. Egorova, Cand. farm. Sciences, assistant of the Department of Internal Medicine No. 1 with a course of clinical Pharmacology of the Medical Academy. S. I. Georgievsky Federal State Autonomous Educational Institution of Higher Education “Crimean Federal ny university named after V. I. Vernadsky “, Simferopol, elena212007@rambler.ru

At present, nuclear medicine technologies associated with the use of radioactive sources for diagnostic and therapeutic purposes are widely introduced into the practice of doctors. Of particular importance is the use in clinical practice of means for determining the state of various organs and systems of the body, such as radiopharmaceuticals (RFP). RFP are drugs that contain one or more radionuclides (radioactive isotopes) in a ready-to-use form. The history of the use of radioactive isotopes in scientific research began in 1913 by D. Hevesi. In 1927, H. L. Blumgart and S. Weiss first used the radioactive isotope radon for diagnostic purposes to determine the blood flow rate.

 The widespread use of drugs containing radionuclides in medicine began in the 1940s. Today, there are about 200 types of RFP of various prices on the world pharmaceutical market, the consumption of which is growing by 10-15% annually. The market leaders are the countries of the Asia-Pacific region, Europe and North America, including the USA. The study of the dynamics of consumption of this group of drugs only in the United States showed that by 2020 the volume of the RFP market, according to forecasts, will amount to 20 billion US dollars, which will be 20 times higher than the indicators of 2001. In the Russian Federation, there is a trend towards an increase in cost , production and use of RFP. According to the State Register of Medicines of the Russian Federation, 22 radiopharmaceuticals for scintigraphy and single-photon emission computed tomography (SPECT), 20 radio kits for immune analysis and 6 radiopharmaceuticals based on 4 ultrashort-lived radionuclides for positron emission tomography were registered. The study by authorized persons for pharmacovigilance of the use of RP in clinical practice showed that about 95% of drugs of this group are used for diagnostic purposes, and 5% for radionuclide therapy.

Diagnostics of diseases using radiopharmaceuticals is based on the principle of indication, which makes it possible to monitor the distribution of the radionuclide included in its composition in the body by external registration of radiation with further study of biological and physiological processes. RPs can selectively accumulate in the intravascular, extracellular and other spaces of the body, which makes it possible to detect structural and functional changes in organs and tissues at the earliest stages of development. The basis of radionuclide therapy is the formation of absorbed doses of ionizing radiation in pathological foci, which leads to damage to vital components of tumor cells and destruction of damaged tissue. It finds its application in the treatment of tumor diseases of the musculoskeletal system, thyroid gland, in the formation of bone metastases of tumors of various localizations.

RFP circulation is carried out in accordance with the requirements established by the legislation in the field of ensuring the radiation safety of the population. RPs can be delivered to health care facilities as ready-to-use forms or as kits for preparation in health care facilities to reduce costs. In the latter case, the RP is prepared in the laboratory from a set of reagents and a radioactive label immediately before use. Order No. 211n of 04/27/2015 “On Approval of the Procedure for the Production of Radiopharmaceutical Medicines Directly in Medical Organizations” regulates the need to manufacture RFP in medical organizations in controlled areas that meet the requirements of sanitary and epidemiological rules and hygienic standards in the field of ensuring radiation safety, at the written request of an authorized employee of a medical organization in accordance with the appointment of the attending physician. An authorized person for pharmacovigilance, in the event of an inspection of a medical facility, must also control this aspect. Approval of the documentation for the manufacture and quality assurance of the RFP containing the manufacturing technology, storage requirements, unitary enterprise

All medicines containing radionuclides require increased attention to their safety profile. This is due to the high risk of exposure of patients to radiation exposure during their use, which suggests the potential for the development of somatic damage or genetic consequences. According to various estimates of authorized persons for pharmacovigilance, the incidence of ADRs when using RPs is from 1 to 6 cases of reactions per 100,000 injections, which makes it possible to conventionally classify such ADRs as relatively rare, regardless of cost. The relatively low rate of development of HP is due to the strict control of the RFP activity, their shelf life, as well as their predominant use in a hospital setting. However, potential risks of developing AD still persist and most often manifest themselves in patients already at the stage of their stay outside medical institutions. In this regard, the monitoring, analysis and assessment of HP of this group of medicinal products by the Pharmacovigilance Authorized Persons required by the Rules of Good Pharmacovigilance Practice contribute to improving the safety of patients exposed to radiation. Analysis of the data on the safety of radiopharmaceuticals showed that the incidence of ADRs when used for diagnostic purposes is significantly lower than when drugs of this group are used in radionuclide therapy of tumors. This is due to the fact that the doses of the administered drugs used to diagnose diseases are significantly lower than the doses used for therapeutic purposes, and, accordingly, HP is most often referred to the category of non-serious and reversible. HPs arising from the use of radiopharmaceuticals for therapeutic purposes are more often classified as serious, which is associated with tissue damage with large doses of ionizing radiation, which increases the cost of treatment in the brow.