The difluoromethyl functionality has proven useful in drug discovery, as it can modulate the properties of bioactive molecules. For PET imaging, this structural motif has been largely underexploited in (pre)clinical radiotracers due to a lack of user-friendly radiosynthetic routes. This Minireview provides an overview of the challenges facing radiochemists and summarises the efforts made to date to access 18F-difluoromethyl-containing radiotracers. Two distinct approaches have prevailed, the first of which relies on 18F-fluorination. A second approach consists of a 18F-difluoromethylation process, which uses 18F-labelled reagents capable of releasing key reactive intermediates such as the [18F]CF2H radical or [18F]difluorocarbene. Finally, we provide an outlook for future directions in the radiosynthesis of [18F]CF2H compounds and their application in tracer radiosynthesis.

中文翻译：

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18F-二氟甲基：挑战、影响和展望

二氟甲基官能团已被证明在药物发现中有用，因为它可以调节生物活性分子的特性。对于 PET 成像，由于缺乏用户友好的放射合成途径，这种结构基序在临床前放射性示踪剂中基本上没有得到充分利用。本小型回顾概述了放射化学家面临的挑战，并总结了迄今为止为获取含 18F-二氟甲基的放射性示踪剂所做的努力。目前流行两种不同的方法，第一种方法依赖于 18F-氟化。第二种方法包括 18F-二氟甲基化过程，该过程使用能够释放关键反应中间体（例如 [18F]CF2H 自由基或[18F]二氟卡宾）的 18F 标记试剂。最后，我们对[18F]CF2H化合物的放射合成及其在示踪剂放射合成中的应用的未来方向进行了展望。