One-pot radiosynthesis of O-[18F]fluoromethyl-D-tyrosine via intra-molecular nucleophilic 18F-fluorination with 1,2,3-triazolium triflate salt precursor

A radiolabeled amino acid O-[F-18]fluoromethyl-D-tyrosine (D-[F-18]FMT) has been reported to show high tumor uptake. However, introduction of [F-18]fluoromethyl group was difficult and was an issue to be solved. We solved it by using a precursor containing 1,2,3-triazolium salt. D-[F-18]FMT was synthesized from (R) - 1-((4-(2-((tert-butoxycarbonyl)arnino) 3-((3,4-dimethylbenzyl)oxy) - 3-oxopropyl)phenoxy)methyl) - 3-methyl-4-phenyl- 1H-1,2,3-triazol-3-ium trifluoromethanesulfonate via intra-molecular F-18-fluorination and subsequent removal of the protecting groups. The total synthesis time was 65 min (including purification) and the overall radiochemical yield was 9% based on the isolated product (not decay-corrected). The resulting D-[F-18]FMT was obtained with high radiochemical purity (> 99%) and specific activity (100-150 GBq/pmol). D-[F-18]FMT also achieved excellent results in pharmacological evaluation such as stability test and protein binding assay. We expect that this simple one-pot labeling method would help using D-[F-18]FMT more widely.