6-[18F]fluoro-L-dopa probes dopamine turnover rates in central dopaminergic structures.
6-[18F]Fluoro-L-DOPA (FDOPA) cerebral kinetics and metabolism were correlated in normal primates (Macaca nemestrina) and primates with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced unilateral Parkinsonism. Application of a tracer kinetic model to positron emission tomography (PET) data indicated that the model allows reliable estimation of FDOPA blood brain barrier transport, decarboxylation and release of stored 6-[18F]fluorodopamine (FDA) radioactivity in normal striatum (k4 = 0.005/min, turnover half-time greater than or equal to 2 hr), in agreement with biochemical data. PET scans of MPTP treated monkeys revealed 40-50% reduction in total striatal activity in comparison with pre-MPTP scans. Monkey brain biochemical analysis revealed that the reduction in activity was mainly due to a decrease in FDA and its metabolites, 6[18F]fluorohomovanillic (FHVA) and 6-[18F]fluoro-3, 4-dihydroxyphenylacetic acid (FDOPAC). The remaining activity in tissue was 3-0-methyl-6-[18F]fluoro-L-DOPA (3-OMFD) of peripheral origin. The (FHVA + FDOPAC)/FDA ratio was 1:2 in normal putamen and greater than or equal to 6:1 in the lesioned putamen, indicative of a dramatic increase in turnover of FDA. Both kinetic and biochemical data indicate that FDOPA labels a slow turnover rate pool of dopamine in rat and primate brain. This turnover rate for stored dopamine (DA) is accelerated with dopaminergic cell losses (e.g., MPTP-induced Parkinsonism).
Barrio
J R
JR
Department of Radiological Sciences, UCLA School of Medicine 90024.
Huang
S C
SC
Melega
W P
WP
Yu
D C
DC
Hoffman
J M
JM
Schneider
J S
JS
Satyamurthy
N
N
Mazziotta
J C
JC
Phelps
M E
ME
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D001923:Brain Chemistry / Q000502:physiology*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D004298:Dopamine / Q000493:pharmacokinetics* / Q000502:physiology; D005456:Fluorescent Dyes; D005462:Fluorine Radioisotopes; D008254:Macaca nemestrina; D008297:Male; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism; D011699:Putamen / Q000378:metabolism; D014055:Tomography, Emission-Computed
D005456:Fluorescent Dyes; D005462:Fluorine Radioisotopes; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine