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

Abstract

The unnatural isotope fluorine-18 (¹⁸F) is used as a positron emitter in molecular imaging. Currently, many potentially useful ¹⁸F-labeled probe molecules are inaccessible for imaging because no fluorination chemistry is available to make them. The 110-minute half-life of ¹⁸F requires rapid syntheses for which [¹⁸F]fluoride is the preferred source of fluorine because of its practical access and suitable isotope enrichment. However, conventional [¹⁸F]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 ¹⁸F-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.