The radiolytic degradation of vector molecules is a major factor affecting the shelf life of therapeutic radiopharmaceuticals. The development of time-stable dosage forms of radiopharmaceuticals is the key to their successful implementation in clinical practice. Using [¹⁷⁷Lu]Lu-PSMA-617 molecule as an example, the time dependence of the change in radiochemical purity (RCP, %) under radiolysis conditions was studied. The dependence of [¹⁷⁷Lu]Lu-PSMA-617 radiolysis on parameters such as time, radionuclide activity, buffer agent concentration, precursor amount, and preparation volume was evaluated. It was shown that the absorbed dose was the dominant factor influencing the RCP. The RCP value is inversely proportional to the absorbed dose in the [¹⁷⁷Lu]Lu-PSMA-617 preparation and has an exponential dependence. The lutetium-177 dose factor ψ (Gy·mL·MBq⁻¹) and PSMA-617 concentration-dependent dose constant κ (Gy⁻¹) were evaluated for absorbed dose estimation via computer modeling, chemical dosimetry, and radiochemical purity monitoring under various conditions. The further refinement and application of the dependencies found can be useful for predicting the RCP value at the stage of optimizing the composition of the finished dosage form of therapeutic radiopharmaceuticals. The influence of the buffer agent (sodium acetate) concentration on [¹⁷⁷Lu]Lu-PSMA-617 radiolytic degradation was shown and should be considered both when developing a dosage form, and when comparing the results of independent studies. The effectiveness of the addition of various stabilizing agents, such as DMSA, cysteine, gentisic acid, vanillin, methionine, adenine, dobesilic acid, thymine, uracil, nicotinamide, meglumine, and mannitol, in suppressing the effects of radiolysis was evaluated.

Introduction. The symptoms of Parkinson's disease are mainly associated with the formation of intraneuronal protein inclusions with Lewy bodies, and the progressive loss of dopaminergic neurons of the Substantia nigra and their axons. Existing diagnostic criteria for the diagnosis of Parkinson's disease often take into account symptoms occurring in the later stages of the disease. Thus, for a more accurate diagnosis in the early stages, it is necessary to confirm pathologic changes in brain tissue by molecular imaging methods such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). At the same time SPECT is a more accessible method of diagnostics of neurodegenerative diseases in comparison with PET, because of the possibility to obtain medical radionuclides for SPECT imaging using mobile generator systems, in particular ⁹⁹Mo/^99mTc generator. Among the formulations based on ^99mTc and tropane derivatives proposed for dopamine transporter (DAT) imaging, [^99mTc]Tc-TRODAT-1 (technetium-99m-labeled tropantiol) is the most effective. Currently, various compositions of the freeze-dried kits for the synthesis of [^99mTc]Tc-TRODAT-1 have been proposed, facilitating the process of its production in situ, which, together with the availability of technetium-99m generator in a healthcare facility, as well as favorable pharmacokinetics, makes [^99mTc]Tc-TRODAT-1 a drug of choice for routine use in clinical practice.Text. In this review, various approaches to design and optimize the composition of the freeze-dried kits for the synthesis of [^99mTc]Tc-TRODAT-1, including the amount and ratio of active ingredient and excipients, synthesis conditions, in particular the temperature regime, synthesis time and pH of the reaction mixture, have been considered.Conclusion. Development and optimization of the composition of the freeze-dried kits for the synthesis of [^99mTc]Tc-TRODAT-1 is an urgent task in the context of improving its use in clinical practice. Based on the published data, clear dependencies can be traced, which may form the basis for further development and optimization of the composition of the freeze-dried kits for [^99mTc]Tc-TRODAT-1 synthesis for the diagnosis of Parkinson's disease and other neurodegenerative diseases by SPECT in the Russian Federation.

Introduction. The use of radiopharmaceuticals for targeted radionuclide therapy (TRT), the efficacy of which was established during clinical trials, is safe and effective for various pathological conditions, including cancer. The main feature of therapeutic radiopharmaceuticals (RPs) is the use of β^–- and α-emitting radionuclides (RNs) in the finished dosage form (FD). Among the radionuclides used for radionuclide therapy, lutetium-177 is currently one of the most popular in clinical practice because of its chemical and nuclear characteristics. The list of RPs based on lutetium-177 is constantly expanding, and Lutathera® ([¹⁷⁷Lu]Lu-DOTA-TATE) and Pluvicto™ ([¹⁷⁷Lu]Lu-PSMA-617) have been approved for clinical use in several countries.Text. Because of the high activity of RNs in a single dose of therapeutic RPs (up to 8 GBq in a monodose for ¹⁷⁷Lu), ionizing radiation of the used RNs leads to a decrease in RPs quality owing to radiolytic degradation of the vector molecule. This leads to a decreased specific accumulation of radioactivity in the foci of pathology, reduced therapeutic effect, and potentially increases the risk of radiotoxicity to non-target organs and tissues. The degree and intensity of radiolytic degradation of the vector molecule and, consequently, the shelf life of RPs depend on many factors, among which the activity concentration of the radionuclide in the preparation, its half-life, and the energy of the emitted particles are the most important. To suppress the effects of radiolysis, various excipients with antioxidant (radioprotective) properties were introduced into the compositions of the finished dosage forms. Among the substances studied, the most popular were gentisic acid, ascorbic acid, and ethanol. In this work, the advantages and disadvantages of various antioxidants and their combinations used in therapeutic RPs were considered in lutetium-177 preparations.Conclusion. Selection of the optimal composition of the dosage form is an urgent task, as it will ensure high-quality RPs both at the time of preparation and during the shelf life and delivery to the end user, which will greatly facilitate the use and centralized supply of therapeutic RPs. The necessity of creating a unified approach for the selection of antioxidants at the pharmaceutical development stage of radiopharmaceuticals is shown. For this purpose, an approach combining studies of radical reaction kinetics with studies of radiation-chemical yields of radiolysis products under identical or maximally similar conditions with subsequent verification of the stability of RPs dosage form seems to be very promising and has proven to be effective. In contrast, the empirical approach, which implies the selection of radioprotectors based on a direct study of their influence on the preservation of the level of radiochemical purity, is suboptimal because of the high market value of both radionuclides and non-radioactive precursors.