Efficient automated syntheses of high specific activity 6-[18F]fluorodopamine using a diaryliodonium salt precursor

6-[F-18]Fluorodopamine (6-[F-18]F-DA) is a positron emission tomography radiopharmaceutical used to image sympathetic cardiac innervation and neuroendocrine tumors. Imaging with 6-[F-18]F-DA is constrained, in part, by the bioactivity and neurotoxicity of 6-[F-19]fluorodopamine. Furthermore, routine access to this radiotracer is limited by the inherent difficulty of incorporation of [F-18]fluoride into electron-rich aromatic substrates. We describe the simple and direct preparation of high specific activity (SA) 6-[F-18]F-DA from no-carrier-added (n.c.a.) [F-18]fluoride. Incorporation of n.c.a. [F-18]fluoride into a diaryliodonium salt precursor was achieved in 50-75% radiochemical yields (decay corrected to end of bombardment). Synthesis of 6-[F-18]F-DA on the IBA Synthera (R) and GE TRACERlab FX-FN automated platforms gave 6-[F-18]F-DA in >99% chemical and radiochemical purities after HPLC purification. The final non-corrected yields of 6-[F-18]F-DA were 25 +/- 4% (n=4, 65min) and 31 +/- 6% (n=3, 75min) using the Synthera and TRACERlab modules, respectively. Efficient access to high SA 6-[F-18]F-DA from a diaryliodonium salt precursor and n.c.a. [F-18]fluoride is provided by a relatively subtle change in reaction conditions - replacement of a polar aprotic solvent (acetonitrile) with a relatively nonpolar solvent (toluene) during the critical radiofluorination reaction. Implementation of this process on common radiochemistry platforms should make 6-[F-18]F-DA readily available to the wider imaging community.