Trifluoromethanesulfonic acid, an alternative solvent medium for the direct electrophilic fluorination of DOPA:: new syntheses of 6-[18F]fluoro-L-DOPA and 6-[18F]fluoro-D-DOPA

Previous work from this laboratory has shown that the direct fluorination of 3, 4-dihydroxy-phenyl-L-alanine (L-DOPA) in anhydrous HF (aHF) or BF3/HF with F-2 is an efficient method for the synthesis of 6-fluoro-L-DOPA. Since then, F-18-labeled 6-fluoro-L-DOPA ([F-18]6-fluoro-L-DOPA) has been used to study presynaptic dopaminergic function in the human brain and to monitor gastrointestinal carcinoid tumors. This work demonstrates that the reactivity and selectivity of F-2 toward L-DOPA in CF3SO3H is comparable with that in aHF. This new synthetic procedure has led to the production of [F-18]fluoro-L-DOPA and [F-18]fluoro-D-DOPA isomers in 17 +/- 2% radiochemical yields (decay corrected with respect to [F-18]F-2). The 2- and 6-FDOPA isomers were separated by HPLC and subsequently characterized by F-19 NMR spectroscopy. The corresponding [F-18]-FDOPA enantiomers have been obtained in clinically useful quantities by a synthetic approach that avoids the use of aHF. Copyright (C) 2007 John Wiley & Sons, Ltd.