Бифункциональные хелаторы к катиону галлия

Цели. Химия радионуклидов ⁶⁷Ga и ⁶⁸Ga играет одну из ключевых ролей в ядерной медици­не для применения в радиофармпрепаратах, в частности, в неинвазивных методах мо­лекулярной визуализации in vivo. Использование радиометаллов для мечения биомолекул обычно требует использования бифункциональных хелаторов, которые, кроме полиден­татного фрагмента, координирующего металл, содержат функциональную группу для ковалентного связывания с вектором-мишенью. Цели данного обзора – проанализировать накопленный к настоящему времени экспериментальный материал, касающийся разра­ботки и применения в медицинских исследованиях бифункциональных хелаторов к кати­ону галлия, а также выявить и проанализировать основные требования, предъявляемые к структуре хелатора и его комплексов с ⁶⁸Ga, необходимые для создания эффективных фармакологических препаратов на его основе.

Результаты. Рассмотрены макроциклические бифункциональные хелаторы, образую­щие стабильные in vivo комплексы с ⁶⁸Ga, а также ациклические хелаторы, преимуще­ство которых заключается в более быстрой кинетике комплексообразования, что явля­ется ключевым фактором, учитывающим короткий период полураспада ⁶⁸Ga. Проведена оценка достоинств и недостатков обоих типов лигандов. Кроме того, осуществлен кри­тический анализ констант связывания и условий образования комплексов. Рассмотрены примеры влияния природы металлического комплекса (геометрия, липофильность, об­щий заряд) на биораспределение целевых радиофармацевтических препаратов.

Выводы. Несмотря на достигнутые успехи в рассмотренных направлениях создания би­фунциональных хелаторов, по-прежнему важной остается проблема корреляции хими­ческой структуры радиофармпрепаратов на основе металлов с их поведением in vivo. В этом отношении сравнительные исследования препаратов, имеющих идентичный вектор нацеливания, но включающих разные бифункциональные хелатируюшие агенты, могут помочь в дальнейшем выявлении влияния металл-хелатного фрагмента на фар­макокинетику. В целом можно отметить, что для создания эффективного бифункци­онального хелатирующего агента нужно принимать во внимание целую совокупность факторов, включающую стабильность и инертность хелатора и его комплексов в физиологических условиях, липофильность, кинетику комплексообразования, селективность хеланирования, комбинаторность базовой структуры, а также экономические аспекты: доступность сырья, сложность схемы синтеза.

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