Lee, EunsungKamlet, Adam SethPowers, David C.Neumann, Constanze N.Boursalian, GregoryFuruya, TakeruChoi, Daniel C.Hooker, JacobRitter, Tobias2012-02-172011Lee, Eunsung, Adam Seth Kamlet, David C. Powers, Constanze Nicole Neumann, Gregory Bagrad Boursalian, Takeru Furuya, Daniel C. Choi, Jacob M. Hooker, and Tobias Ritter. 2011. A fluoride-derived electrophilic late-stage fluorination reagent for PET imaging. Science 334(6056): 639-642.0036-80751095-9203http://nrs.harvard.edu/urn-3:HUL.InstRepos:8187682The 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.en-USchemistryfluoridesfluorine radioisotopeshalogenationreagentsindicatorschemical synthesisorganometallic compoundspalladiumpositron-emission tomographyJournal Article2012-02-1710.1126/science.1212625