Alcohol-Supported Cu-Mediated ¹⁸F-Fluorination of Iodonium Salts under "Minimalist" Conditions.

Abstract

In the era of personalized precision medicine, positron emission tomography (PET) and related hybrid methods like PET/CT and PET/MRI gain recognition as indispensable tools of clinical diagnostics. A broader implementation of these imaging modalities in clinical routine is closely dependent on the increased availability of established and emerging PET-tracers, which in turn could be accessible by the development of simple, reliable, and efficient radiolabeling procedures. A further requirement is a c GMP production of imaging probes in automated synthesis modules. Herein, a novel protocol for the efficient preparation of ¹⁸F-labeled aromatics via Cu-mediated radiofluorination of (aryl)(mesityl)iodonium salts without the need of evaporation steps is described. Labeled aromatics were prepared in high radiochemical yields simply by heating of iodonium [¹⁸F]fluorides with the Cu-mediator in methanolic DMF. The iodonium [¹⁸F]fluorides were prepared by direct elution of ¹⁸F - from an anion exchange resin with solutions of the corresponding precursors in MeOH/DMF. The practicality of the novel method was confirmed by the racemization-free production of radiolabeled fluorophenylalanines, including hitherto unknown 3-[¹⁸F]FPhe, in 22-69% isolated radiochemical yields as well as its direct implementation into a remote-controlled synthesis unit.