A new precursor for the preparation of 6-[18F]Fluoro-l-m-tyrosine ([18F]FMT): efficient synthesis and comparison of radiolabeling

Abstract

For the electrophilic preparation of 6-[18F]fluoro-L-m-tyrosine ([18F]FMT), a PET tracer for measuring changes in dopaminergic function in movement disorders, a novel precursor, N-(tert-butoxycarbonyl)-3-(tert-butoxycarbonyloxy)-6-trimethylstannnyl-L-phenylalanine ethyl ester, was synthesized in four steps and 26% yield starting from L-m-tyrosine. [18F]FMT produced by two methods at two institutions was comparable in both radiochemical yield, 25-26%, and quality (chemical, enantiomeric, and radiochemical purity and specific activity) as that obtained with the original N-trifluoroacetyl-3-acetyl-6-trimethylstannyl-L-m-tyrosine ethyl ester [18F]FMT precursor.

Radical scavengers: A practical solution to the reproducibility issue in the fluoridation of diaryliodonium salts

“…(1) is a well established example of this and is a radioligand for the study of brain dopaminergic neuron density in movement disorders, such as Parkinson's disease [18,19]. In addition 6-[ 18 F]fluoro-m-tyrosine (2) has proven a useful alternative to L-6-[ 18 F]-fluoroDOPA as it remains a substrate for aromatic L-amino acid decarboxylase (producing the phenethylamine derivatives) yet is not subject to methylation by catecholamine-O-methyltransferase allowing improved contrast in PET images [20] (Scheme 1).…”

Dopamine and the Cognitive Downside of a Promised Bonus

“…FMT synthesis has been described previously (VanBrocklin et al, 2004). FMT is comparable with [ 18 F]fluorodopa, with the exception that it is not a substrate for O-methylation in the periphery and therefore provides higher signal-to-noise images (Jordan et al, 1997).…”

Dorsal Striatal Dopamine, Food Preference and Health Perception in Humans

“…PET imaging and FMT binding were performed at Lawrence Berkeley National Laboratory, as described previously [17]. FMT is a substrate of aromatic L-amino acid decarboxylase (AADC), a dopamine-synthesizing enzyme whose activity corresponds to the capacity of dopaminergic neurons to synthesize dopamine [13] and has been shown to be indicative of pre-synaptic dopamine synthesis capacity [18].…”