pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»10.33380/2305-2066-2025-14-1-1882pharmjournal-2001Research ArticleФАРМАЦЕВТИЧЕСКАЯ ТЕХНОЛОГИЯPHARMACEUTICAL TECHNOLOGYФармацевтическая разработка и практические подходы к синтезу радиофармацевтического лекарственного препарата на основе тропантиола ([99mTc]Tc-TRODAT-1) для диагностики нейродегенеративных заболеваний (обзор)Pharmaceutical development and practical approach to synthesis of tropantiol radiopharmaceutical ([99mTc]Tc-TRODAT-1) for diagnostic of neurodegenerative diseases (review)https://orcid.org/0000-0002-6638-4292ПавленкоЕ. П.PavlenkoE. P.

123098, г. Москва, ул. Живописная, д. 46

46, Zhivopisnaya str., Moscow, 123098

pavlenko.katya@yandex.ruhttps://orcid.org/0000-0002-9508-2840МалышеваА. О.MalyshevaA. O.

123098, г. Москва, ул. Живописная, д. 46

46, Zhivopisnaya str., Moscow, 123098

https://orcid.org/0000-0003-4810-4346ЛаренковА. А.LarenkovA. A.

123098, г. Москва, ул. Живописная, д. 46

46, Zhivopisnaya str., Moscow, 123098

anton.larenkov@gmail.comФедеральное государственное бюджетное учреждение «Государственный научный центр Российской Федерации – Федеральный медицинский биофизический центр им. А. И. Бурназяна» (ФГБУ ГНЦ ФМБЦ им. А.И. Бурназяна ФМБА России)State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency202513122024141112126Copyright © Павленко Е.П., Малышева А.О., Ларенков А.А., 20252025Павленко Е.П., Малышева А.О., Ларенков А.А.Pavlenko E.P., Malysheva A.O., Larenkov A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/2001Введение

Введение. Симптомы болезни Паркинсона в основном связаны с образованием белковых внутринейрональных включений с тельцами Леви, а также прогрессирующей потерей дофаминергических нейронов черной субстанции (Substantia nigra) и их аксонов. Существующие диагностические критерии для постановки диагноза «болезнь Паркинсона» зачастую учитывают симптомы, возникающие на поздних стадиях заболевания. Таким образом, для более точной постановки диагноза на ранних стадиях необходимо подтвердить патологические изменения в тканях головного мозга методами молекулярной визуализации, такими как позитронно-эмиссионная томография (ПЭТ) и однофотонная эмиссионная компьютерная томография (ОФЭКТ). При этом ОФЭКТ является более доступным методом диагностики нейродегенеративных заболеваний по сравнению с ПЭТ из-за возможности получения медицинских радионуклидов для визуализации методом ОФЭКТ с помощью мобильных генераторных систем, в частности генератора 99Mo/99mTc. Среди препаратов на основе 99mTc и производных тропана, предложенных для визуализации транспортеров дофамина (DAT), наиболее эффективным является [99mTc]Tc-TRODAT-1 (меченный технецием-99m тропантиол). На данный момент предложены различные составы готовых наборов реагентов в форме лиофилизатов для синтеза [99mTc]Tc-TRODAT-1, облегчающих процесс его изготовления на месте применения, что вместе с доступностью генератора техенция-99m в медицинском учреждении, а также оптимальной фармакокинетикой делает [99mTc]Tc-TRODAT-1 препаратом выбора для рутинного применения в клинической практике.

Текст

Текст. В данном обзоре были рассмотрены различные подходы к разработке и оптимизации состава готовых наборов реагентов для синтеза [99mTc]Tc-TRODAT-1 (лиофилизатов), включая количество и соотношение активного вещества и вспомогательных веществ, условия синтеза препарата, в частности температурный режим, время синтеза и pH реакционной смеси.

Заключение

Заключение. Разработка и оптимизация состава готовых наборов лиофилизатов для синтеза [99mTc]Tc-TRODAT-1 является актуальной задачей в контексте совершенствования его применения в клинической практике. На основании опубликованных данных прослеживаются четкие зависимости, которые могут лечь в основу дальнейшей разработки и оптимизации состава готовых наборов лиофилизатов для синтеза [99mTc]Tc-TRODAT-1 для диагностики болезни Паркинсона и других нейродегенеративных заболеваний методом ОФЭКТ в Российской Федерации.

Introduction

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

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

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.

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The authors declare that there are no conflicts of interest present.