Pharmaceutical development and practical approach to synthesis of tropantiol radiopharmaceutical ([99mTc]Tc-TRODAT-1) for diagnostic of neurodegenerative diseases (review)

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 99 Mo/ 99m Tc generator. Among the formulations based on 99m Tc and tropane derivatives proposed for dopamine transporter (DAT) imaging, [ 99m Tc]Tc-TRODAT-1 (technetium-99m-labeled tropantiol) is the most effective. Currently, various compositions of the freeze-dried kits for the synthesis of [ 99m Tc]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 [ 99m Tc]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 [ 99m Tc]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 [ 99m Tc]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 [ 99m Tc]Tc-TRODAT-1 synthesis for the diagnosis of Parkinson's disease and other neurodegenerative diseases by SPECT in the Russian Federation.