6-[F-18]FLUORO-L-M-TYROSINE - METABOLISM, POSITRON EMISSION TOMOGRAPHY KINETICS, AND 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE LESIONS IN PRIMATES

The tracer 6-[F-18]fluoro-L-m-tyrosine (FMT) was studied with regard t o its biochemistry and kinetics, as well as its utility in evaluating brain dopaminergic function in primates before and after 1-methyl-4-ph enyl-1,2,3,6-tetrahydropyridine (MPTP) treatment using positron emissi on tomography (PET). Plasma analysis of FMT and its F18-labeled metabo lites 6-fluoro-3-hydroxyphenylacetic acid (FPAC) and 6-fluoro-3-hydrox yphenylethylamine (FMA) during PET scanning enabled kinetic analysis o f FMT uptake, A separate study examined brain FMT metabolism in MPTP-n aive 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 dop aminergic areas such as caudate and putamen. This bilateral FMT signal was disrupted after unilateral intracarotid artery (ICA) MPTP infusio n which reduced ipsilateral striatal activity. A three compartment thr ee kinetic rate constant model for FMT uptake revealed reduced FMT dec arboxylation (k(3)) in ipsilateral caudate and putamen after unilatera l MPTP although a further decrease was not evident after intravenous M PTP. FPAC was the major F-18 species in all brain regions except in ce rebellum where FMT was predominant 60 min post-mortem FPAC was most co ncentrated in dopaminergic areas whereas lower levels occurred in area s containing few dopamine terminals. These data demonstrate preferenti al FMT metabolism and F-18 retention in dopaminergic tissue and suppor t the use of FMT to evaluate normal and abnormal dopaminergic function . (C) 1997 Elsevier Science B.V.