Copper-Mediated Aromatic Radiofluorination Revisited: Efficient Production of PET Tracers on a Preparative Scale

Two novel methods for copper-mediated aromatic nucleophilic radiofluorination were recently reported. Evaluation of these methods reveals that, although both are efficient in small-scale experiments, they are inoperative for the production of positron emission tomography (PET) tracers. Since high base content turned out to be responsible for low radiochemical conversions, a low base protocol has been developed which affords F-18-labeled arenes from diary-liodonium salts and aryl pinacol boronates in reasonable yields. Furthermore, implementation of our minimalist approach to the copper-mediated [F-18]-fluorination of (mesity-l)(aryl) iodonium salts allows the preparation of F-18-labeled arenes in excellent RCCs. The novel radiofluorination method circumvents time-consuming azeotropic drying and avoids the utilization of base and other additives, such as cryptands. Furthermore, this procedure enables the production of clinically relevant PET tracers; [F-18] FDA, 4-[F-18] FPhe, and [F-18]DAA1106 are obtained in good isolated radiochemical yields. Additionally, [F-18] DAA1106 has been evaluated in a rat stroke model and demonstrates excellent potential for visualization of translocator protein 18 kDa overexpression associated with neuroinflammation after ischemic stroke.