Synthesis of [18F]RO41-0960, a potent catechol-O-methyltransferase inhibitor, for PET studies

Ro41-0960 (3,4-dihydroxy-5-nitro-2'-fluorobenzophenone) is a potent, fluorine containing COMT inhibitor. In order to map catechol-O-methyltransferase (COMT) in vivo with PET, no-carrier-added [18F]Ro41-0960 was synthesized by the nucleophilic aromatic substitution of [18F]fluoride for 2'-nitro on 3,4-dimethoxy-5,2'-dimethoxy-5,2'-dinitrobenzophenone, followed by hydrolysis with HBr. During the course of this study it was found that [18F]fluoromethane ([18F]CH3F) was generated as the side product of nucleophilic aromatic substitution reaction. Various precursors with different hydroxyl protecting groups were then investigated for the effects on this side reaction. (Author)