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 (18)F-labeled arenes from diaryliodonium salts and aryl pinacol boronates in reasonable yields. Furthermore, implementation of our "minimalist" approach to the copper-mediated [(18)F]-fluorination of (mesityl)(aryl)iodonium salts allows the preparation of (18)F-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; [(18)F]FDA, 4-[(18)F]FPhe, and [(18)F]DAA1106 are obtained in good isolated radiochemical yields. Additionally, [(18)F]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.