Chemistry Research Laboratory, University of Oxford, Mansfield Road, OX1 3TA Oxford, UK.
Bioorg Med Chem. 2012 Jan 1;20(1):324-9. doi: 10.1016/j.bmc.2011.10.084. Epub 2011 Nov 6.
Radiopharmaceuticals for nuclear imaging are essentially targeting molecules, labeled with short-lived radionuclides (e.g., F-18 for PET). A significant drawback of radiopharmaceuticals development is the difficulty to access radiolabeled molecule libraries for initial in vitro evaluation, as radiolabeling has to be optimized for each individual molecule. The present paper discloses a method for preparing libraries of (18)F-labeled radiopharmaceuticals using both the fluorous-based (18)F-radiochemistry and the Huisgen 1,3-dipolar (click) conjugation reaction. As a proof of concept, this approach allowed us to obtain a series of readily accessible (18)F-radiolabeled nitroaromatic molecules, for exploring their structure-activity relationship and further in vitro evaluation of their hypoxic selectivity.
核医学成像用放射性药物本质上是靶向分子，用短寿命放射性核素（例如 F-18 用于 PET）标记。放射性药物开发的一个显著缺点是难以获得用于初始体外评估的放射性标记分子文库，因为必须针对每个单独的分子优化放射性标记。本文公开了一种使用基于氟的（18）F 放射性化学和 Huisgen 1,3-偶极（点击）共轭反应制备（18）F 标记放射性药物文库的方法。作为概念验证，这种方法使我们能够获得一系列易于获得的（18）F 放射性标记的硝基芳烃分子，以探索它们的构效关系，并进一步进行体外缺氧选择性评估。
