The lack of simple, efficient [<sup>18</sup>F]fluorination processes and new target-specific organofluorine probes remains the major challenge of fluorine-18-based positron emission tomography (PET). We report here a fast isotopic
exchange method for the radiosynthesis of aryl [<sup>18</sup>F]fluorosulfate
based PET agents enabled by the emerging sulfur fluoride exchange (SuFEx) click chemistry. The
method has been applied to the fully-automated <sup>18</sup>F-radiolabeling of
twenty-five structurally diverse aryl fluorosulfates with excellent
radiochemical yield (83–100%) and high molar activity (up to 281 GBq µmol<sup>–1</sup>)
at room temperature in 30 seconds. The purification of radiotracers requires no
time-consuming high-performance liquid chromatography (HPLC), but rather a
simple cartridge filtration. The utility of aryl [<sup>18</sup>F]fluorosulfate is demonstrated by the <i>in vivo</i> tumor imaging by targeting poly(ADP-ribose) polymerase 1 (PARP1).
