Automated radiochemical synthesis of [18F]FBEM: a thiol reactive synthon for radiofluorination of peptides and proteins.

The automated radiochemical synthesis of N-[2-(4-[(18)F]fluorobenzamido)ethyl]maleimide ([(18)F]FBEM, IUPAC name: N-maleoylethyl-4-[(18)F]fluorobenzamide), a prosthetic group for radiolabeling the free sulfhydryl groups of peptides and proteins, is herein described. 4-[(18)F]fluorobenzoic acid was first prepared by nucleophilic displacement of a trimethylammonium moiety on a pentamethylbenzyl benzoate ester with [(18)F]fluoride. In the second step the ester was cleaved under acidic conditions. Finally, 4-[(18)F]fluorobenzoic acid was coupled to N-(2-aminoethyl)maleimide using diethylcyanophosphate and diisopropylethyl amine. Following high-performance liquid chromatography (HPLC) purification, [(18)F]FBEM was obtained in 17.3±7.1% yield (not decay corrected) in approximately 95 min. Isolation from the HPLC eluate and preparation for subsequent use, which was conducted manually, required an additional 10-15 min. The measured specific activity for three batches was 181.3, 251.6, and 351.5 GBq/μmol at the end of bombardment (EOB).