6-[F-18]FLUORO-L-DOPA PROBES DOPAMINE TURNOVER RATES IN CENTRAL DOPAMINERGIC STRUCTURES

被引：48

作者：

BARRIO, JR

HUANG, SC

MELEGA, WP

YU, DC

HOFFMAN, JM

SCHNEIDER, JS

SATYAMURTHY, N

MAZZIOTTA, JC

PHELPS, ME

机构：

[1] UNIV CALIF LOS ANGELES,SCH MED,DEPT PHARMACOL,LOS ANGELES,CA 90024

[2] UNIV CALIF LOS ANGELES,SCH MED,NUCL MED LAB,LOS ANGELES,CA 90024

来源：

JOURNAL OF NEUROSCIENCE RESEARCH | 1990年 / 27卷 / 04期

关键词：

POSITRON EMISSION TOMOGRAPHY; BRAIN DOPAMINE POOLS; CEREBRAL KINETICS/METABOLISM;

D O I：

10.1002/jnr.490270408

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

6-[F-18]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-[F-18]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[F-18]fluorohomovanillic (FHVA) and 6-[F-18]fluoro-3, 4-dihydroxyphenylacetic acid (FDOPAC). The remaining activity in tissue was 3-0-methyl-6-[F-18]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).

引用

页码：487 / 493

页数：7

共 36 条

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