Barrio J R, Huang S C, Melega W P, Yu D C, Hoffman J M, Schneider J S, Satyamurthy N, Mazziotta J C, Phelps M E
Department of Radiological Sciences, UCLA School of Medicine 90024.
J Neurosci Res. 1990 Dec;27(4):487-93. doi: 10.1002/jnr.490270408.
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).
在正常灵长类动物（食蟹猴）和1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的单侧帕金森病灵长类动物中，对6-[18F]氟-L-多巴（FDOPA）的脑动力学和代谢进行了相关性研究。将示踪动力学模型应用于正电子发射断层扫描（PET）数据表明，该模型能够可靠地估计正常纹状体中FDOPA的血脑屏障转运、脱羧作用以及储存的6-[18F]氟多巴胺（FDA）放射性的释放（k4 = 0.005/分钟，周转半衰期大于或等于2小时），这与生化数据一致。对MPTP处理的猴子进行的PET扫描显示，与MPTP处理前的扫描相比，纹状体总活性降低了40 - 50%。猴子脑生化分析表明，活性降低主要是由于FDA及其代谢产物6-[18F]氟高香草酸（FHVA）和6-[18F]氟-3,4-二羟基苯乙酸（FDOPAC）的减少。组织中剩余的活性是外周来源的3-0-甲基-6-[18F]氟-L-多巴（3-OMFD）。在正常壳核中，（FHVA + FDOPAC）/FDA的比值为1:2，而在受损壳核中该比值大于或等于6:1，这表明FDA的周转显著增加。动力学和生化数据均表明，FDOPA标记了大鼠和灵长类动物脑中多巴胺的一个周转缓慢速率池。随着多巴胺能细胞损失（例如，MPTP诱导的帕金森病），储存多巴胺（DA）的这种周转速率会加快。
