Original Articles
Journal of Cerebral Blood Flow & Metabolism (1999) 19, 278–287; doi:10.1097/00004647-199903000-00006
Evaluation of Dopaminergic Presynaptic Integrity: 6-[18F]Fluoro-L-Dopa Versus 6-[18F]Fluoro-L-m-Tyrosine
This work was supported by the Medical Research Council of Canada GR-13296.
D J Doudet, G L-Y Chan, S Jivan, O T DeJesus*, E G McGeer, C English, T J Ruth and J E Holden*
- Department of Medicine, Division of Neurology and Kinsmen Laboratory of Neurological Research and TRIUMF, University of British Columbia, Vancouver, British Columbia, Canada
- *Department of Medical Physics, University of Wisconsin, Madison, Wisconsin, U.S.A.
Correspondence: DJ Doudet, Room M36, Purdy Pavilion, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
Received 12 March 1998; Revised 16 July 1998; Accepted 22 July 1998.
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 (kloss), and an index of "effective turnover" of dopamine (kloss/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 kloss or kloss/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.
Keywords:
6-[18F]L-dopa, 6-[18F]L-m-Tyrosine, Dopamine neurons, Positron emission tomography, Dopamine turnover
Abbreviations:
AAAD, aromatic amino acid decarboxylase; COMT, catechol O-methyltransferase; DA, dopamine; FDA, 6-[18F]fluoro-dopamine; 6FDOPA, 6-[18F]fluoro-L-dopa; FDOPAC, 6-fluoro-dihydroxyphenylacetic acid; FHVA, 6-fluoro-homovanillic acid; FMA, 6-[18F]fluoro-m-tyramine; 6FMT, 6-[18F]fluoro-L-m-tyrosine; FPAC, 6-[18F]fluoro-hydroxyphenylacetic acid; Kc, rate of uptake of tracer into striatum using activity of occipital cortex as input function; Ki, rate of uptake of tracer into striatum using arterial input function; kloss, rate of loss of striatal radioactivity; kloss/Ki, index of effective turnover; MAO, monoamine oxidase; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 3OMFDOPA, 3-O-methyl-[18F]fluoro-L-dopa; PET, positron emission tomography; ROI, region of interest

