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6‐[ 18 F]fluoro‐ L ‐DOPA PET studies of the turnover of dopamine in MPTP‐induced parkinsonism in monkeys
Author(s) -
Doudet Doris J.,
Chan Grace L.Y.,
Holden James E.,
Mcgeer Edith G.,
Aigner Thomas A.,
Wyatt Richard J.,
Ruth Thomas J.
Publication year - 1998
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199807)29:3<225::aid-syn4>3.0.co;2-8
Subject(s) - mptp , parkinsonism , dopamine , neuroscience , pharmacology , chemistry , medicine , psychology , dopaminergic , disease
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‐[ 18 F]fluoro‐ L ‐DOPA (FDOPA), and an extension of the graphical method of analysis, we measured the striatal FDOPA uptake rate constant, K i , 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 /K i . Compared to normal controls, K i 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. Synapse 29:225–232, 1998. © 1998 Wiley‐Liss, Inc.