6-[18F]fluoro-L-m-tyrosine: metabolism, positron emission tomography kinetics, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine lesions in primates.

ABSTRACT

The tracer 6-[18F]fluoro-L-m-tyrosine (FMT) was studied with regard to its biochemistry and kinetics, as well as its utility in evaluating brain dopaminergic function in primates before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment using positron emission tomography (PET). Plasma analysis of FMT and its F18-labeled metabolites 6-fluoro-3-hydroxyphenylacetic acid (FPAC) and 6-fluoro-3-hydroxyphenylethylamine (FMA) during PET scanning enabled kinetic analysis of FMT uptake. A separate study examined brain FMT metabolism in MPTP-naive monkeys euthanized 60 or 120 min after FMT injection. Almost 60% of total plasma F-18 activity was associated with FPAC and FMA 120 min after FMT injection. The FMT signal accumulated preferentially in dopaminergic areas such as caudate and putamen. This bilateral FMT signal was disrupted after unilateral intracarotid artery (ICA) MPTP infusion which reduced ipsilateral striatal activity. A three compartment three kinetic rate constant model for FMT uptake revealed reduced FMT decarboxylation (k3) in ipsilateral caudate and putamen after unilateral MPTP although a further decrease was not evident after intravenous MPTP. FPAC was the major F-18 species in all brain regions except in cerebellum where FMT was predominant 60 min post-mortem. FPAC was most concentrated in dopaminergic areas whereas lower levels occurred in areas containing few dopamine terminals. These data demonstrate preferential FMT metabolism and F-18 retention in dopaminergic tissue and support the use of FMT to evaluate normal and abnormal dopaminergic function.