PHARMACOKINETICS OF PLASMA 6-[F-18]FLUORO-L-3,4-DIHYDROXYPHENYLALANINE ([F-18]FDOPA) IN HUMANS
PHARMACOKINETICS OF PLASMA 6-[F-18]FLUORO-L-3,4-DIHYDROXYPHENYLALANINE ([F-18]FDOPA) IN HUMANS
复制标题
DOI：
10.1038/jcbfm.1993.85
复制
发表时间：
1993-07-01
影响因子：
6.3
通讯作者：
GJEDDE, A
中科院分区：
文献类型：
--
作者：
CUMMING, P;LEGER, GC;GJEDDE, A
与天然多巴一样，[F-18]-6-氟-L-3，4-二羟基苯丙氨酸（[F-18]FDOPA）也会发生甲基化和脱羧作用。为了确定[F-18]FDOPA代谢物的形成和消除速率，通过高效液相色谱法（HPLC）分析了接受正电子发射断层扫描（PET）研究的人类受试者的血浆。除主要代谢物O-甲基][F-18]FDOPA（OMe[F-18]FDOPA）外，还在卡比多巴预治疗受试者的血浆中检测到两种脱羧代谢物。示踪剂注射后90 min内各代谢物的浓度可描述为[F-18]FDOPA浓度和两个速率常数的函数; k 0，形成速率，和k-1，清除速率。由总血浆活性曲线和测定的速率常数生成的血浆代谢物时间序列与HPLC分馏法测定的实际浓度非常一致。使用k 0（0.011 +/- 0.002 min-1）和k-1（0.010 +/- 0.003 min-1）的群体平均值生成“模拟"血浆曲线。将测量和生成的血浆曲线用作估算[F-18]FDOPA在脑中的分配和脱羧系数的输入。使用从正常群体平均值的传递系数生成的输入函数没有引入系统误差到酶活性的估计中。然而，这些估计值在患者中的高度变异性排除了使用该技术作为个体HPLC测量的替代方法。
Like native DOPA, [F-18]-6-fluoro-L-3,4-dihydroxyphenylalanine ([F-18]FDOPA) is subject to methylation and decarboxylation. To determine the rates of formation and elimination of [F-18]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][F-18]FDOPA (OMe[F-18]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 [F-18]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 [F-18]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.