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.