Quantitative in vivo receptor binding III: Tracer kinetic modeling of muscarinic cholinergic receptor binding.
Quantitative in vivo receptor binding III: Tracer kinetic modeling of muscarinic cholinergic receptor binding.
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定量体内受体结合 III：毒蕈碱胆碱能受体结合的示踪动力学模型。
DOI：
10.1073/pnas.82.19.6711
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发表时间：
1985
影响因子：
11.1
通讯作者：
Agranoff,BW
中科院分区：
文献类型：
--
作者：
Frey,KA;Hichwa,RD;Ehrenkaufer,RL;Agranoff,BW
建立了一种示踪动力学方法，用于体内测定高亲和力放射性配体与中枢神经系统受体的结合。配体被认为存在于三个脑池中，分别对应于游离、非特异性结合和特异性结合示踪剂。这些环境，除了血管内示踪剂，在体内配体分布的房室模型相互关联。该模型的数学描述的推导，它允许确定区域血脑屏障的渗透性，非特异性结合，受体-配体协会的速率，结合配体的解离速率，从动脉血和组织示踪剂浓度的时间过程。引入术语“游离受体密度”来描述通过该方法测量的受体群体。该技术适用于在体内测定区域毒蕈碱乙酰胆碱受体在大鼠中，使用[3 H]东莨菪碱。游离毒蕈碱受体密度的动力学估计与从先前的体内和体外平衡结合研究中获得的结合能力大体一致。然而，在纹状体中，游离受体密度的动力学估计值小于新皮层中的估计值--这是来自平衡测定的这些区域的等级排序的逆转。一个简化的模型，是适用于示踪剂，不容易从特定的结合位点在实验期间解离。在这种情况下，特异性示踪剂结合可以通过在静脉推注后的单个时间点测量组织配体浓度来准确地确定，前提是已知局部脑血流量。这种推导具有潜在的临床应用，因为它将允许通过正电子发射断层成像在人脑中构建区域游离受体密度的定量图像图。
A tracer kinetic method is developed for the in vivo estimation of high-affinity radioligand binding to central nervous system receptors. Ligand is considered to exist in three brain pools corresponding to free, nonspecifically bound, and specifically bound tracer. These environments, in addition to that of intravascular tracer, are interrelated by a compartmental model of in vivo ligand distribution. A mathematical description of the model is derived, which allows determination of regional blood-brain barrier permeability, nonspecific binding, the rate of receptor-ligand association, and the rate of dissociation of bound ligand, from the time courses of arterial blood and tissue tracer concentrations. The term "free receptor density" is introduced to describe the receptor population measured by this method. The technique is applied to the in vivo determination of regional muscarinic acetylcholine receptors in the rat, with the use of [3H]scopolamine. Kinetic estimates of free muscarinic receptor density are in general agreement with binding capacities obtained from previous in vivo and in vitro equilibrium binding studies. In the striatum, however, kinetic estimates of free receptor density are less than those in the neocortex--a reversal of the rank ordering of these regions derived from equilibrium determinations. A simplified model is presented that is applicable to tracers that do not readily dissociate from specific binding sites during the experimental period. In this instance, specific tracer binding may be accurately determined by measuring tissue ligand concentration at a single time point after bolus intravenous injection, providing that regional cerebral blood flow is known. This derivation has potential clinical application, because it will permit construction of quantitative pictorial maps of regional free receptor densities in the human brain by means of positron emission tomographic imaging.