Evaluation of dopaminergic presynaptic integrity: 6-[18F]fluoro-L-dopa versus 6-[18F]fluoro-L-m-tyrosine

Abstract

The effectiveness of 6-[18F]fluoro-L-m-tyrosine (6FMT) to evaluate dopamine presynaptic integrity was compared to that of 6-[18F]fluoro-L-dopa (6FDOPA) in vivo by positron emission tomography (PET). Six normal and six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned monkeys received 6FDOPA and 6FMT PET scans on separate occasions with identical scanning protocols. Four measures, the rate of uptake of tracer into striatum using either the arterial input function (Ki) or the activity in the occipital cortex as the input function (Kc), the rate of loss of striatal radioactivity (k(loss)), and an index of "effective turnover" of dopamine (k(loss)/Ki), were obtained for both tracers during extended PET studies. 6-[18F]Fluoro-L-m-tyrosine was as effective as 6FDOPA in separating normals from MPTP-lesioned subjects on the basis of the uptake rate constants Ki and Kc. However, in contrast to 6FDOPA, it was not possible to differentiate the normal from the lesioned animal using k(loss) or k(loss)/Ki for 6FMT. Thus, FMT appears to be a reasonable, highly specific tracer for studying the activity of aromatic dopa decarboxylase enzyme as an index of presynaptic integrity. However, if one is interested in investigating further the metabolic pathway and obtaining an in vivo estimate of the effective turnover of dopamine (after pharmacologic manipulation, for example), 6FDOPA remains the tracer of choice.