Фармацевтическая разработка и практические подходы к синтезу радиофармацевтического лекарственного препарата на основе тропантиола ([^99mTc]Tc-TRODAT-1) для диагностики нейродегенеративных заболеваний (обзор)

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. 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. 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.

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