Novel observations with FDOPA-PET imaging after early nigrostriatal damage.
Striatal 6-[18F]fluoro-L-DOPA (FDOPA) kinetic rate constants were measured by positron emission tomography (PET) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (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 moderate reductions (10-35%) in dopaminergic neurons, where the percent of cell loss was proportional to the amount of MPTP given. Striatal DA and metabolite 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. All animals injected with a single dose of MPTP showed no overt signs of parkinsonism. In contrast, DA and metabolite concentrations in the substantia nigra 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 pathway to the neurotoxic effects of MPTP. The percent change in FDOPA uptake (Ki) and decarboyxlation (k3) after MPTP showed significant positive correlations to striatal DA levels, but not to the number of dopaminergic neurons. This suggests that FDOPA is a good index of striatal DA levels.
Yee
R E
RE
Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, California 90095-6948, USA.
Irwin
I
I
Milonas
C
C
Stout
D B
DB
Huang
S C
SC
Shoghi-Jadid
K
K
Satyamurthy
N
N
Delanney
L E
LE
Togasaki
D M
DM
Farahani
K F
KF
Delfani
K
K
Janson
A M
AM
Phelps
M E
ME
Langston
J W
JW
Barrio
J R
JR
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D004298:Dopamine / Q000172:deficiency*; D005260:Female; D005462:Fluorine Radioisotopes; D008297:Male; D009434:Neural Pathways; D009498:Neurotoxins; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D012453:Saimiri; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D009498:Neurotoxins; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine