Simplified radiolabeling process toward rapid photoredox-catalyzed aryl 18F-fluorination and PET tracer development

In this work, we established a simplified photoredox-mediated labeling system that allows the rapid aryl ¹⁸ F-fluorination of electron-neutral and -rich arenes via ¹⁹ F- ¹⁸ F exchange or/and deoxyfluorination. Notably, this aryl radiofluorination method excludes the cumbersome azeotropic drying procedure and is scalable with the whole eluted ¹⁸ F- beyond portion synthesis. The nonaqueous tetrabutylammonium perchlorate (TBAP) solution was identified as an ideal neutral eluent to balance the elution and labeling efficiency in combination with a HPO ₄ ^2- preconditioned anion-exchange resin (AER). Base-sensitive substrates like alkyl halide, tetrazine, and lipophilic cations were able to be directly aryl ¹⁸ F-labeled under the weak basic conditions. Moreover, this azeotropic drying-free photolabeling method was successfully implemented on a commercial automatic radiosynthesis module. Furthermore, a broad range of unnatural amino-acid derivatives were composed and aryl ¹⁸ F-labeled under the current system, and the arylglycine derivative ¹⁸ F-FMPG was found to be a promising PET agent targeting amino acid transporters. Taken together, the mild labeling conditions combined with the simplicity of the reaction setup from all commercially available reagents and inexpensive equipment guarantees the repeatability and wide adoption of this aryl ¹⁸ F-fluorination method for PET agents and drug discovery.