Novel observations with FDOPA-PET imaging after early nigrostriatal damage

Striatal 6-[F-18]fluoro-L-DOPA (FDOPA) kinetic rate constants were measured by positron emission tomography (PET) in 1-methyl-4-phenyl-1,2,3,6-tetrahy dropyridine (MPTP)-treated squirrel monkeys. After scanning, stereological counts of dopaminergic neurons were done in substantia nigra. and dopamine (DA) and metabolite concentrations were determined in the caudate, putamen, and substantia nigra. Graded doses of MPTP produced animals with mild to m oderate reductions (10-35%) in dopaminergic neurons, where the percent of c ell loss was proportional to the amount of MPTP given. Striatal DA and meta bolite concentrations were relatively unchanged in animals given 1.0 and 1. 5 mg/kg of MPTP, but were significantly reduced after 2.0 mg/kg of MPTP. Al l animals injected with a single dose of MPTP showed no overt signs of park insonism. In contrast, DA and metabolite concentrations in the substantia n igra were significantly reduced for all MPTP-treated animals. Reduction of dopaminergic indices in the substantia nigra did not parallel reductions in the striatum, indicating differential sensitivity of the nigrostriatal pat hway to the neurotoxic effects of MPTP. The percent change in FDOPA uptake (Ki) and decarboyxlation (k(3)) after MPTP showed significant positive corr elations to striatal DA levels, but not to the number of dopaminergic neuro ns. This suggests that FDOPA is a good index of striatal DA levels. (C) 200 1 Movement Disorder Society.