[C-11] TROPANYL BENZILATE BINDING TO MUSCARINIC CHOLINERGIC RECEPTORS - METHODOLOGY AND KINETIC MODELING ALTERNATIVES
[C-11] TROPANYL BENZILATE BINDING TO MUSCARINIC CHOLINERGIC RECEPTORS - METHODOLOGY AND KINETIC MODELING ALTERNATIVES
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DOI：
10.1038/jcbfm.1994.13
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发表时间：
1994-01-01
影响因子：
6.3
通讯作者：
KUHL, DE
中科院分区：
文献类型：
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作者：
KOEPPE, RA;FREY, KA;KUHL, DE
用拮抗剂[C-11]苯甲酸托吡酯([C-11]TRB)和正电子发射断层扫描(PET)对脑内M受体进行了定量研究。对动力学建模备选方案进行了研究，目的是确定一种分析方法，提供稳定的受体测量，同时避免因模型复杂性的不适当降低而产生的偏差。对6名年轻的正常志愿者进行动态正电子发射计算机断层扫描。评估了几种产生相对受体密度测量的建模方法：(A)使用相对示踪剂浓度值的一次“晚期”扫描；(B)从图形分析(Patlak图)估计的斜率；(C)两室两参数模型(转运和总配体分布体积)；(D)使用固定于小脑值的自由+非特异性分布体积dv‘的三室两参数模型；(E)运输的早期扫描，dv’的固定值，以及结合速率常数的一次晚期扫描；和(F)三室三参数模型。计算机模拟和PET扫描结果都表明，所有方法提供的受体密度指数测量具有与体外测量相同的等级顺序。过于简化的方法(方法1和方法2)与保留更大模型复杂性的方法(方法3-6)相比，在估计的受体密度指数和已知的受体密度之间产生了更高度的非线性关系。然而，对于更复杂的方法，噪声传播到接收器测量中的量更大。可靠的受体密度信息可以从动力学的[C-11]TRB PET研究中获得，方法3-5为估计相对M受体密度提供了最合适的模型复杂性水平。
Quantitative estimation of cerebral muscarinic receptors was investigated with the use of the antagonist [C-11]tropanyl benzilate ([C-11]TRB) and positron emission tomography (PET). Kinetic modeling alternatives were examined with the goal of identifying an analysis method providing stable receptor measures, yet avoiding biases from inappropriate reductions in model complexity. Dynamic PET scans were performed on six young normal volunteers. Several modeling approaches yielding relative receptor density measures were evaluated: (a) a single ''late'' scan using relative tracer concentration values; (b) a slope estimate from graphic analysis (Patlak plot); (c) a two-compartment, two-parameter model (transport and total ligand distribution volume); (d) a three-compartment, two-parameter model using the free + nonspecific distribution volume, DV', fixed to the cerebellar value; (e) an early scan for transport, a fixed value for DV', and a single late scan for the binding rate constant; and (f) a three-compartment, three-parameter model. Both computer simulations and PET scan results indicate all methods provide receptor density index measures with the same rank order as in vitro measures. Oversimplified approaches (methods 1 and 2) yield a more highly nonlinear relation between the estimated receptor density index and the known receptor density than do methods retaining greater model complexity (methods 3-6). However, noise propagation into the receptor measure is greater for the more complex methods. Reliable receptor density information can be obtained from kinetic [C-11]TRB PET studies, with methods 3-5 providing the most appropriate levels of model complexity for estimates of relative muscarinic receptor density.