Cumming P, Léger G C, Kuwabara H, Gjedde A
Positron Imaging Laboratory, McConnell Brain Imaging Center, Montreal Neurological Institute, Canada.
J Cereb Blood Flow Metab. 1993 Jul;13(4):668-75. doi: 10.1038/jcbfm.1993.85.
Like native DOPA, [18F]-6-fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) is subject to methylation and decarboxylation. To determine the rates of formation and elimination of [18F]FDOPA metabolites, plasma from human subjects undergoing positron emission tomographic (PET) studies was analyzed by high-performance liquid chromatography (HPLC). In addition to the principal metabolite O-methyl-[18F]FDOPA (OMe[18F]FDOPA), two decarboxylated metabolites were detected in plasma from carbidopa pretreated subjects. The concentrations of each metabolite during 90 min following tracer injection could be described as a function of the concentration of [18F]FDOPA, and two rate constants; k0, the rate of formation, and k-1, the rate of clearance. Plasma metabolite time series generated from total plasma activity curves and measured rate constants were in close agreement with the actual concentrations determined by HPLC fractionation. Population means for k0 (0.011 +/- 0.002 min-1) and k-1 (0.010 +/- 0.003 min-1) were used to generate "simulated" plasma curves. The measured and generated plasma curves were used as inputs for estimation of partition and decarboxylation coefficients of [18F]FDOPA in brain. The use of generated input functions from normal population means of transfer coefficients did not introduce a systematic error into the estimate of the enzyme activity. However, the high variability of these estimates in patients precludes the use of this technique as an alterative to individual HPLC measurements.
与天然多巴一样，[18F]-6-氟-L-3,4-二羟基苯丙氨酸（[18F]FDOPA）会发生甲基化和脱羧反应。为了确定[18F]FDOPA代谢物的生成和消除速率，对接受正电子发射断层扫描（PET）研究的人类受试者的血浆进行了高效液相色谱（HPLC）分析。除了主要代谢物O-甲基-[18F]FDOPA（OMe[18F]FDOPA）外，在接受卡比多巴预处理的受试者的血浆中还检测到两种脱羧代谢物。示踪剂注射后90分钟内每种代谢物的浓度可以描述为[18F]FDOPA浓度和两个速率常数的函数；k0为生成速率，k-1为清除速率。由总血浆活性曲线生成的血浆代谢物时间序列和测得的速率常数与通过HPLC分级分离确定的实际浓度密切一致。k0（0.011±0.002 min-1）和k-1（0.010±0.003 min-1）的总体均值用于生成“模拟”血浆曲线。测得的和生成的血浆曲线被用作估算[18F]FDOPA在脑中的分配系数和脱羧系数的输入值。使用来自转移系数正常总体均值生成的输入函数并未在酶活性估算中引入系统误差。然而，这些估算值在患者中的高变异性使得该技术无法替代个体HPLC测量。
