Melega W P, Luxen A, Perlmutter M M, Nissenson C H, Phelps M E, Barrio J R
Department of Radiological Sciences, UCLA School of Medicine 90024.
Biochem Pharmacol. 1990 Jun 15;39(12):1853-60. doi: 10.1016/0006-2952(90)90601-g.
In vivo double-label experiments in rats were designed to correlate the peripheral and cerebral metabolism of 6-[18F]fluoro-L-DOPA [( 18F]FDOPA) with that of [3H]L-DOPA. Authentic samples of the major [18F]FDOPA metabolites were synthesized to identify the 18F-labeled metabolites. After carbidopa pretreatment and intravenous administration of the compound, the products of peripheral metabolism in plasma were analyzed at times from 3 to 60 min. In the periphery, amine conjugates were detected but they accounted for less than 15% of the total radioactivity; the major metabolites were 3-O-methyl-6-[18F]fluoro-L-DOPA and 3-O-methyl-[3H]L-DOPA. The rate and extent of 3-O-methylation of [18F]FDOPA exceeded that of [3H]L-DOPA. Both 3-O-methylated products entered the striatum and cerebellum where they contributed significant but uniform activity. Analysis of cerebral metabolism in these structures indicated a linear accumulation of total radioactivity: a striatum/cerebellum ratio of 2 was observed by 60 min. 6-[18F]Fluorodopamine (35%) and [3H]dopamine (55%) were the major metabolites formed in the striatum: however, the methylated [18F]FDOPA and [3H]DOPA products of predominantly peripheral origin represented 55% (18F) and 35% (3H) of the total radioactivity respectively. Other [3H]dopamine metabolites and their 18F-labeled analogs represented less than 10-15% at all times analyzed. The cerebellum radioactivity was composed only of [18F]FDOPA, [3H]DOPA and their 3-O-methylated products. These data will serve as the basis for the development of kinetic models of [18F]FDOPA metabolism that can be applied to the evaluation of central dopamine biochemistry with positron emission tomography in humans.
在大鼠体内进行了双标记实验，旨在将6-[18F]氟-L-多巴（[18F]FDOPA）的外周和脑代谢与[3H]L-多巴的代谢相关联。合成了主要[18F]FDOPA代谢物的真实样品，以鉴定18F标记的代谢物。在卡比多巴预处理并静脉注射该化合物后，在3至60分钟的时间点分析血浆中外周代谢产物。在外周，检测到胺结合物，但它们占总放射性的比例不到15%；主要代谢物是3-O-甲基-6-[18F]氟-L-多巴和3-O-甲基-[3H]L-多巴。[18F]FDOPA的3-O-甲基化速率和程度超过了[3H]L-多巴。两种3-O-甲基化产物都进入纹状体和小脑，在那里它们产生了显著但均匀的活性。对这些结构中的脑代谢分析表明总放射性呈线性积累：到60分钟时观察到纹状体/小脑比值为2。6-[18F]氟多巴胺（35%）和[3H]多巴胺（55%）是纹状体中形成的主要代谢物：然而，主要源自外周的甲基化[18F]FDOPA和[3H]多巴产物分别占总放射性的55%（18F）和35%（3H）。在所有分析时间点，其他[3H]多巴胺代谢物及其18F标记类似物占比均小于10 - 15%。小脑放射性仅由[18F]FDOPA、[3H]多巴及其3-O-甲基化产物组成。这些数据将作为开发[18F]FDOPA代谢动力学模型的基础，该模型可用于通过正电子发射断层扫描评估人体中枢多巴胺生物化学。
