6-[F-18]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 dop amine (DA) and describes its application to the evaluation of DA funct ion in normal monkeys and monkeys with 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (MPTP)induced lesions of the DA nigro-striatal pathway. Using positron emission tomography with the tracer of presynaptic DA f unction, 6-[F-18]fluoro-L-DOPA (FDOPA), and an extension of the graphi cal method of analysis, we measured the striatal FDOPA uptake rate con stant, K-i, and the rate of reversibility of FDOPA trapping k(loss) in normal and MPTP-treated monkeys, either neurologically normal or disp laying a parkinsonian symptomatology. An index of effective DA turnove r 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 mon keys. The index of DA turnover was significantly increased in the monk eys displaying a parkinsonian symptomatology as compared to the contro ls and the neurologically normal MPTP-treated monkeys. The DA turnover index was also significantly increased in the neurologically normal M PTP-lesioned animals compared to normals. This suggests that an increa se in DA turnover develops early in the disease process and may be one of the compensatory mechanisms partly responsible for the delay in th e development of the clinical manifestations in Parkinson's disease. ( C) 1998 Wiley-Liss, Inc.