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

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Science (Impact Factor: 33.61). 11/2011; 334(6056):639-42. DOI: 10.1126/science.1212625
Source: PubMed


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.

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    • "We recently reported a conceptually different arene radiofluorination reaction that relies on C–F bond formation at a transition metal center [24]. The novelty of the method consists of [18F]fluoride capture to form an electrophilic fluorination reagent that could be used for late-stage fluorination. "
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