GRAPHICAL ANALYSIS OF REVERSIBLE RADIOLIGAND BINDING FROM TIME ACTIVITY MEASUREMENTS APPLIED TO [N-C-11-METHYL]-(-)-COCAINE PET STUDIES IN HUMAN-SUBJECTS
GRAPHICAL ANALYSIS OF REVERSIBLE RADIOLIGAND BINDING FROM TIME ACTIVITY MEASUREMENTS APPLIED TO [N-C-11-METHYL]-(-)-COCAINE PET STUDIES IN HUMAN-SUBJECTS
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DOI：
10.1038/jcbfm.1990.127
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发表时间：
1990-09-01
影响因子：
6.3
通讯作者：
CHRISTMAN, DR
中科院分区：
文献类型：
--
作者：
LOGAN, J;FOWLER, JS;CHRISTMAN, DR
本文介绍了一种适用于可逆结合受体或酶的配体的图形分析方法，该方法在注射放射性标记示踪剂后需要多次同时测量血浆和组织的放射性。它表明，有一个时间t. intg。之后，intg toROI（t“）dt”/ROI（t）对intg toCp（t“）dt”/ROI（t）的曲线（其中ROI和Cp分别是描述组织放射性和血浆放射性变化的时间函数）是线性的，斜率对应于配体加血浆体积Vp的稳态空间。对于二室模型，斜率由. + VP，其中。是分配系数，截距是-1/[k2（1 + Vp/λ）]。对于三室模型，斜率为.（1 + Bmax/Kd）+Vp，截距为- {（1 + Bmax/Kd/k2 + [koff（1 + Kd/Bmax）]-1} [1 +Vp/k2]。（1 + Bmax/Kd）]-1（其中Bmax表示配体结合位点的浓度，Kd是配体-结合位点复合物的平衡解离常数，koff（k4）是配体-结合位点解离常数，k2是从组织到血浆的转移常数）。该图解法提供了斜率的Bmax/Kd比值，用于与相同参数的体外测量值进行比较。它还提供了一种简单、快速的方法，用于比较单个受试者重复测量的再现性，用于纵向或药物干预方案，或用于比较受试者之间的实验结果。虽然当ROI/Cp恒定时，该图的线性保持不变，但可以表明，对于许多系统，在此之前的某个时间有效地达到线性。该分析已应用于正常人志愿者中[N-甲基11 C]-（-）-可卡因（[11 C]可卡因）研究的数据，并将结果与标准非线性最小二乘分析进行比较。可卡因的高亲和性结合位点的Bmax/Kd的计算值为0.62 ±。0.20，与文献值一致。
A graphical method of analysis applicable to ligands that bind reversibly to receptors or enzymes requiring the simultaneous measurement of plasma and tissue radioactivities for multiple times after the injection of a radiolabeled tracer is presented. It is shown that there is a time t.intg. after which a plot of .intg.toROI(t'')dt''/ROI(t) versus .intg.toCp(t'')dt''/ROI(t) (where ROI and Cp are functions of time describing the variation of tissue radioactivity and plasma radioactivity, respectively) is linear with a slope that corresponds to the steady-state space of the ligand plus the plasma volume, Vp. For a two-compartment model, the slope is given by .lambda. + Vp, where .lambda. is the partition coefficient and the intercept is -1/[k2(1 + Vp/.lambda.)]. For a three-compartment model, the slope is .lambda.(1 + Bmax/Kd)+Vp and the intercept is - { (1 + Bmax/Kd/k2 + [koff (1 + Kd/Bmax)]-1} [1 +Vp/.lambda.(1 + Bmax/Kd)]-1 (where Bmax represents the concentration of ligand binding sites and Kd the equilibrium dissociation constant of the ligand-binding site complex, koff (k4) the ligand-binding site dissociation constant, and k2 is the transfer constant from tissue to plasma). This graphical method provides the ratio Bmax/Kd from the slope for comparison with in vitro measures of the same parameter. It also provides an easy, rapid method for comparison of the reproducibility of repeated measures in a single subject, for longitudinal or drug intervention protocols, or for comparing experimental results between subjects. Although the linearity of this plot holds when ROI/Cp is constant, it can be shown that, for many systems, linearity is effectively reached some time before this. This analysis has been applied to data from [N-methyl11C]-(-)-cocaine ([11C]cocaine) studies in normal human volunteers and the results are compared to the standard non-linear least-squares analysis. The calculated value of Bmax/Kd for the high-affinity binding site for cocaine is 0.62 .+-. 0.20, in agreement with literature values.