Cumming P, Kuwabara H, Gjedde A
Montreal Neurological Institute, Québec, Canada.
J Neurochem. 1994 Nov;63(5):1675-82. doi: 10.1046/j.1471-4159.1994.63051675.x.
A previous study of the metabolism of 6-[18F]-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) in rats pretreated with carbidopa contained information amenable to kinetic analysis. Using these data, tracer transfer coefficients and metabolic rate constants were estimated. After intravenous injection, FDOPA in circulation was O-methylated (k0D = 0.055 min-1), and the metabolite (O-methyl-FDOPA) escaped from plasma with a rate constant (k-1M) of 0.01 min-1. The initial clearance of FDOPA to striatum (K1D) was 0.07 ml g-1 min-1, and the equilibrium distribution volume (VeD) was 0.67 ml g-1. The initial clearance of O-methyl-FDOPA to striatum (K1M) was 0.08 ml g-1 min-1, and the equilibrium distribution volume (VeM) was 0.75 ml g-1. The rate constant of FDOPA decarboxylation (k3D) was 0.17 min-1 in striatum. The elimination of 6-[18F]fluorodopamine (FDA) from striatum suggested an apparent rate constant for monoamine oxidase activity (k7') of 0.055 min-1. 6-[18F]Fluorohomovanillic acid (FHVA) was formed from 6-[18F]fluoro-L-3,4-dihydroxyphenylacetic acid with a rate constant (k11) of 0.083 min-1, and FHVA was eliminated from striatum (k9) with a rate constant of 0.12 min-1. The steady-state concentration ratios of FDA and its metabolites were shown to be functions of these rate constants.
先前一项关于用卡比多巴预处理的大鼠体内6-[18F]-氟-L-3,4-二羟基苯丙氨酸（FDOPA）代谢的研究包含了适合进行动力学分析的信息。利用这些数据，估算了示踪剂转移系数和代谢速率常数。静脉注射后，循环中的FDOPA发生O-甲基化（k0D = 0.055分钟-1），代谢产物（O-甲基-FDOPA）以速率常数（k-1M）为0.01分钟-1的速度从血浆中逸出。FDOPA向纹状体的初始清除率（K1D）为0.07毫升·克-1·分钟-1，平衡分布容积（VeD）为0.67毫升·克-1。O-甲基-FDOPA向纹状体的初始清除率（K1M）为0.08毫升·克-1·分钟-1，平衡分布容积（VeM）为0.75毫升·克-1。纹状体中FDOPA脱羧的速率常数（k3D）为0.17分钟-1。纹状体中6-[18F]氟多巴胺（FDA）的消除表明单胺氧化酶活性的表观速率常数（k7'）为0.055分钟-1。6-[18F]氟高香草酸（FHVA）由6-[18F]氟-L-3,4-二羟基苯乙酸以速率常数（k11）为0.083分钟-1形成，FHVA以速率常数为0.12分钟-1从纹状体中消除（k9）。FDA及其代谢产物的稳态浓度比显示为这些速率常数的函数。
