The production and application of radioisotopes and radiopharmaceuticals is a major peaceful application of nuclear science and technology and has opened new gateways for nuclear medicine in critical human diseases. Advances in the production of radioisotopes via nuclear reactors, accelerators, fission, etc. has facilitated the access to these products for Member States. ⁹⁹Mo, ¹³¹I, ¹⁷⁷Lu are among the most essential radioisotopes for nuclear medicine and human health and their production and availability always has been an important theme for professional societies and the International Atomic Energy Agency (IAEA). In the meantime, a large list of theranostic radioisotopes including but not limited to ⁸⁹Zr, ⁶⁸Ga, ²²⁵Ac, Cu-series, Sc-series, Tb-series etc. has provided a powerful toolbox for clinicians and the IAEA is taking steps to ensure their safe and appropriate application in radiopharmacy. The Agency promotes the production and application routes, including research reactors, cyclotrons, linear accelerators, and other cutting-edge methods, according to international and national guidelines and regulations. The IAEA also conducts activities such as Coordinated Research Projects (CRPs), Technical Meetings (TMs), national/regional training courses and conferences, to support and join forces with international professional societies in the development of human resources and research and development activities. Development of databases and freely available publications for all Member States are other useful means to support Member States in radiopharmaceutical sciences.

The fast development of diagnostic and therapeutic radionuclide technologies requires enhanced legislative regulation of radiopharmaceuticals. The article addresses the challenge of classifying radiopharmaceuticals depending on the manufacturing technology, radionuclide properties, and clinical use. The review covers the current legislative and regulatory requirements for radiopharmaceutical medicinal products. It also describes the trends in radiopharmaceutical regulation development in Russia and the Eurasian Economic Union, taking into account the corresponding legislative frameworks.

Radiopharmaceuticals, the medicinal products containing radioactive isotopes, hold a special place among the other medicines. The aim of the study was to analyse regulatory peculiarities of the production and subsequent life cycle of radiopharmaceuticals, associated with the unique physicochemical properties, production process, distribution, and clinical use. The article reviews regulatory decisions adopted in Russia and a number of other countries that, in certain circumstances, allow medical organisations not licensed as manufacturers to compound radiopharmaceuticals for in-house use without marketing authorisation. Unstable isotopes in radiopharmaceuticals reduce the risk of microbial contamination, so the quality control requirements may be relaxed. The described regulatory framework, which came into effect 12 years ago, provided an opportunity for a many-fold increase in the number of radiopharmaceuticals for radionuclide diagnosis and treatment of severe socially significant diseases. In recent years, a number of countries have adopted regulations making it possible to  supply the  radiopharmaceuticals manufactured by medical organisations outside the usual marketing authorisation track to other medical organisations. If adopted in Russia, a similar regulation will further expand the access to effective methods of diagnosis and treatment for patients.

Pharmacokinetic (PK) studies of radiopharmaceuticals (RPs) are distinctive because of small concentrations of active ingredients. Whereas methods applicable to non-RP medicinal products cannot be used for RPs, radionuclide methods can provide an insight into radionuclide behaviour. The aim of the study was to compare approaches to pre-clinical PK evaluation of RPs and other medicinal products. The article describes the main aspects of PK studies of RPs and non-RPs, defining similarities and differences in the conduction of these studies. The authors provided examples from their own PK studies of RPs: one investigating the possibility of using ^99mTc–Zoledronic acid to visualise bone pathologies in patients receiving Zometa^©; and the other demonstrating the advantage of orthotopic xenograft models over heterotopic ones. According to the conclusions, methods based on ionising radiation are undeniably superior to other methods used to study the PK of medicinal products (for example, the former offer a possibility of non-invasive detection of active ingredients in the nano and/or pico range). The data obtained during PK studies can be used to characterise both the safety and functional suitability of RPs.

Pharmacokinetic parameters are important for calculating the absorbed dose; they also provide an indirect measure of the in vivo stability of a radiopharmaceutical. The aim of the study was to determine the excretion rate of the activity of ¹⁷⁷Lu-DOTA-PSMA-617 and MCA 5–10 microns, ¹⁸⁸Re, from the blood and urine of patients undergoing systemic and local radiotherapy in clinical trials. Materials and methods: the study involved radiometry of blood and urine samples of 12 male patients with metastatic prostate cancer and 20 patients of both sexes with chronic synovitis, selected after radiotherapy with the experimental radiopharmaceuticals ¹⁷⁷Lu-DOTA-PSMA-617 and MCA 5–10 microns, ¹⁸⁸Re, respectively. The activity of the samples was measured using a dose calibrator and a gamma counter. Results: the activity of ¹⁷⁷Lu in the blood of patients was 36.0–89.3%, 10.4–55.7%, 14.6–32.8%, 10.6–35.7%, and 7.3–25.1% at 5 minutes and at 1, 3, 6 and 8 hours after the administration of ¹⁷⁷Lu-DOTA-PSMA-617, respectively. The 48-hour urine excretion varied within 34.4–88.8% for ¹⁷⁷Lu-DOTA-PSMA-617 and within 0.15–2.91% for MCA 5–10 microns, ¹⁸⁸Re. Conclusions: the maximum values of ¹⁷⁷Lu-DOTA-PSMA-617 activity in the blood 8 hours after administration (9.6–25.1%) corresponded to the maximum injected activity of the radiopharmaceutical product. The low rate of ¹⁸⁸Re urinary excretion after intra-articular administration of MCA 5–10 microns, ¹⁸⁸Re, is an indirect indication of the quality of the radiopharmaceutical. The obtained pharmacokinetic parameters show high in vivo stability of the ¹⁷⁷Lu and ¹⁸⁸Re medicinal products. The results obtained will be used to calculate absorbed doses in patients.

Deterministic effects of medical exposure to ionising radiation can be associated with both the effectiveness of treatment and adverse drug reactions to it. The latter may drastically deteriorate the quality of life of a patient after radionuclide therapy. In addition, the regulations of the Russian Federation require indicating the effective dose of radiation as a measure of damage (risk), but the presence of a deterministic effect in individual organs and tissues complicates monitoring and recording patient exposure doses. The aim of the study was to investigate the effect of radiopharmaceuticals containing ¹³¹I on the development of secondary nasolacrimal duct obstruction (NLDO). Materials and methods: the study of secondary NLDO predictors analysed medical history data, post-therapy head-and-neck scintigrams, and methods to prepare patients for treatment. It involved sodium iodide, ¹³¹I, formulated as a solution (marketing authorisation number: FS-002065) by the FSUE Federal Center of Nuclear Medicine Projects Design and Development of the FMBA of Russia. Results: the authors unambiguously localised the lacrimal ducts in post-therapy ¹³¹I scintigrams of the head and neck and quantified ¹³¹I uptake ratios for the lacrimal duct area. Also, they identified a set of NLDO predictors: the age of a patient, the administered activity, the administration of recombinant human thyroid-stimulating hormone, the ¹³¹I uptake ratio, etc. The article describes a method for identifying the groups at risk of NLDO following radioiodine therapy for differentiated thyroid cancer. Conclusions: secondary NLDO is a deterministic effect of ¹³¹I exposure. The authors have developed a new method for predicting secondary NLDO by a combination of the patient’s individual parameters and treatment plan; the identified predictors help to personalise radioiodine therapy. The authors suggest the following: to include information on secondary NLDO as a complication of therapy to the SmPC section on undesirable effects; to develop approaches to secondary NLDO prevention; and to improve the algorithms for reporting adverse events in case of delayed manifestation and those for following patients up in the medical organisations having administered the radiopharmaceutical or in other medical organisations being applied to for medical care afterwards.

Theranostics is a promising branch of nuclear medicine that uses radiopharmaceuticals for diagnosis and treatment of cancer, and immunotheranostics is a special area in it. The aim of the study was to summarise the potential of theranostics for visualisation of the tumour microenvironment and elimination of its immunosuppressive components. The article presents up-to-date information on the composition and interaction of various cell subpopulations in the tumour microenvironment, as well as on the role of cancer stem cells in its formation. It describes defects of signalling pathways and potential targets for theranostics of cancer stem cells. Also, the article provides a description of the mechanism of interaction between the tumour and the immune system in the process of carcinogenesis. The review offers a detailed analysis of approaches to assessing the type of tumour microenvironment in order to individualise treatment and develop a rational design of clinical studies of theranostic couples. The authors present their own data on the distribution of subpopulations of lymphocytes and myeloid-derived suppressor cells in patients with metastatic tumours. The authors have considered the nuances of creating and using various molecules for targeted delivery in the development of diagnostic and therapeutic radiopharmaceuticals. The most promising diagnostic and therapeutic isotopes are described from the point of view of assessing the microenvironment and the possibility of influencing it. The article highlights modern and promising methods of pre-targeting to reduce the toxicity and increase the effectiveness of theranostics. Furthermore, having compared the advantages and disadvantages of theranostics with those of other systemic treatment options for metastatic tumours, the authors outline possible ways to overcome the shortcomings of theranostics.

Positron emission tomography coupled with computed tomography (PET/CT) has proven to be highly informative in the diagnosis of various malignant tumours. PET/CT examination takes into account biological and morphological data, which allow accurate tumour localisation and full staging of the disease, respectively. Cervical cancer (CC) is one of the most common, high-mortality cancers in women. The effectiveness of CC treatment depends on early diagnosis, which is connected to the assessment of local tumour spread and metastatic lymph node involvement and to the  detection of disease recurrence. The aim of the study was to  analyse the possibility of using PET/CT with ¹⁸F-FDG for the diagnosis of CC and the evaluation of treatment effectiveness. Additionally, the study aimed to analyse the potential of using other radiopharmaceuticals as biomarkers for the assessment of tumour response. Cervical malignancies are characterised by high glycolytic activity, which explains the superiority of ¹⁸F-FDG PET/CT over other traditional imaging methods in comprehensive diagnosis of patients with CC and, especially, in detecting nodal involvement and distant metastases. Also, ¹⁸F-FDG PET/CT plays an important part in the assessment of treatment effectiveness in CC patients. Further development of ¹⁸F-FDG PET/CT potential in the visualisation of malignant cervical lesions is associated with investigating the possibilities of using other specific radiopharmaceuticals to obtain information about the biological processes that support tumour cell growth: metabolism, proliferative activity, and oxygenation.

Radiochemical purity (RCP) is one of the key quality criteria for radiopharmaceuticals (RPs) used in clinical practice. The results of RCP measurements depend on the analytical technique, as well as detection parameters, which are specific to a particular analytical system. When reviewing literature data on the  synthesis, pharmaceutical development, preclinical and clinical trials of the same radiopharmaceutical by different authors, one may note significant variability in the RCP values obtained. Hence, it is important to carefully select analysis parameters and study their influence on the results. The aim of the study was to compare previously published and self-developed procedures for RCP analysis of ¹⁷⁷Lu-RPs in terms of their efficiency in the  detection and quantification of possible radiochemical impurities, as well as to  determine the  analytical system parameters that have a  significant impact on the interpretation of the analysis results, using [¹⁷⁷Lu]Lu–PSMA-617 as a case study. Materials and methods: the study used samples of [¹⁷⁷Lu]Lu–PSMA-617 with a volume activity of lutetium-177 of 150–4800 MBq/mL, containing 10–100 µmol/L of the PSMA-617 precursor and 30 mmol/L of sodium acetate as a buffering solution (pH 4.5). The samples were tested by high-performance liquid chromatography (HPLC) and thin-layer chromatography in the conditions described in the literature and developed in the course of the work. Results: the study showed a significant influence of the chosen analytical procedure on the results of [¹⁷⁷Lu]Lu–PSMA-617 RCP assessment. The profile of possible radiochemical impurities requires the use of high-resolution HPLC techniques. Conclusions: the analytical procedure developed and applied by the authors is quite effective. The results of RCP assessment are influenced by the detection system parameters, such as the length and inner diameter of the flow cell and the means of analytical signal processing (peak extraction parameters, smoothing parameters, and noise subtraction/suppression). This fact necessitates validation considering the characteristics of a particular analytical system and demonstrates the need to assess interlaboratory precision in the framework of the implementation and verification of analytical procedures.