A Fluoride-Derived Electrophilic Late-Stage Fluorination Reagent for PET Imaging

Abstract

The unnatural isotope fluorine-18 ((^{18}F)) is used as a positron emitter in molecular imaging. Currently, many potentially useful (^{18}F)-labeled probe molecules are inaccessible for imaging because no fluorination chemistry is available to make them. The 110-minute half-life of (^{18}F) requires rapid syntheses for which ([^{18}F])fluoride is the preferred source of fluorine because of its practical access and suitable isotope enrichment. However, conventional ([^{18}F])fluoride chemistry has been limited to nucleophilic fluorination reactions. We report the development of a palladium-based electrophilic fluorination reagent derived from fluoride and its application to the synthesis of aromatic (^{18}F)-labeled molecules via late-stage fluorination. Late-stage fluorination enables the synthesis of conventionally unavailable positron emission tomography (PET) tracers for anticipated applications in pharmaceutical development as well as preclinical and clinical PET imaging.