6-[18F]Fluoro-L-DOPA PET studies of the turnover of dopamine in MPTP-induced parkinsonism in monkeys.
This report describes a method to assess, in vivo, the turnover of dopamine (DA) and describes its application to the evaluation of DA function in normal monkeys and monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced lesions of the DA nigro-striatal pathway. Using positron emission tomography with the tracer of presynaptic DA function, 6-[18F]fluoro-L-DOPA (FDOPA), and an extension of the graphical method of analysis, we measured the striatal FDOPA uptake rate constant, Ki, and the rate of reversibility of FDOPA trapping k(loss) in normal and MPTP-treated monkeys, either neurologically normal or displaying a parkinsonian symptomatology. An index of effective DA turnover was defined as the ratio of k(loss)/Ki. Compared to normal controls, Ki was decreased and k(loss) was increased in the MPTP-lesioned monkeys. The index of DA turnover was significantly increased in the monkeys displaying a parkinsonian symptomatology as compared to the controls and the neurologically normal MPTP-treated monkeys. The DA turnover index was also significantly increased in the neurologically normal MPTP-lesioned animals compared to normals. This suggests that an increase in DA turnover develops early in the disease process and may be one of the compensatory mechanisms partly responsible for the delay in the development of the clinical manifestations in Parkinson's disease.
Doudet
D J
DJ
Department of Medicine, Kinsmen Laboratory of Neurological Research and TRIUMF, University of British Columbia, Vancouver, Canada. ddoudet@interchange.ubc.ca
Chan
G L
GL
Holden
J E
JE
McGeer
E G
EG
Aigner
T A
TA
Wyatt
R J
RJ
Ruth
T J
TJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004298:Dopamine / Q000378:metabolism*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000378:metabolism*; D012016:Reference Values; D014055:Tomography, Emission-Computed
C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine