Correlation of striatal fluorodopa uptake in the MPTP monkey with dopaminergic indices.
Striatal 18F-6-fluorodopa (FD) uptake constants were measured by positron emission tomography in (1) normal cynomolgus monkeys and (2) a series of cynomolgus and rhesus monkeys that had received intracarotid infusions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After the animals were killed, the number and average size of dopaminergic neurons in the substantia nigra pars compacta were measured. Striatal levels of dopamine and its metabolites, and the striatal activities of the dopaminergic synthetic enzymes, were also determined. The striatal FD uptake constants showed highly significant positive correlations with both number and size of dopaminergic neurons, indicating atrophy of surviving neurons in MPTP-treated animals. The uptake constants also showed significant positive correlations with striatal levels of dopamine, total catecholamines, and the activities of the synthetic enzymes. Both histochemical and biochemical data on tyrosine hydroxylase suggested some contralateral enzyme loss in these MPTP-treated monkeys, as well as decreased enzyme activity in surviving neurons on the lesioned side. However, residual enzyme activities were apparently not rate limiting to striatal FD uptake. It is concluded that PET-FD measurements by positron emission tomography provide a good index of the integrity of the nigrostriatal pathway.
Pate
B D
BD
Neurodegenerative Disorders Centre, University of British Columbia, Vancouver, Canada.
Kawamata
T
T
Yamada
T
T
McGeer
E G
EG
Hewitt
K A
KA
Snow
B J
BJ
Ruth
T J
TJ
Calne
D B
DB
D000818:Animals; D001692:Biological Transport; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D020267:MPTP Poisoning; D008252:Macaca fascicularis; D008297:Male; D009474:Neurons / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods
D005462:Fluorine Radioisotopes; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D004298:Dopamine