6-[18F]fluoro-L-DOPA PET studies of the turnover of dopamine in MPTP-induced parkinsonism in monkeys
Article first published online: 7 DEC 1998
Copyright © 1998 Wiley-Liss, Inc.
Volume 29, Issue 3, pages 225–232, July 1998
How to Cite
Doudet, D. J., Chan, G. L.Y., Holden, J. E., Mcgeer, E. G., Aigner, T. A., Wyatt, R. J. and Ruth, T. J. (1998), 6-[18F]fluoro-L-DOPA PET studies of the turnover of dopamine in MPTP-induced parkinsonism in monkeys. Synapse, 29: 225–232. doi: 10.1002/(SICI)1098-2396(199807)29:3<225::AID-SYN4>3.0.CO;2-8
- Issue published online: 7 DEC 1998
- Article first published online: 7 DEC 1998
- Manuscript Accepted: 15 SEP 1997
- Manuscript Received: 7 JUN 1997
- Medical Research Council of Canada
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 kloss 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 kloss/Ki. Compared to normal controls, Ki was decreased and kloss 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. Synapse 29:225–232, 1998. © 1998 Wiley-Liss, Inc.