Quantitative analysis for estimating binding potential of the peripheral benzodiazepine receptor with [11C] DAA1106
Quantitative analysis for estimating binding potential of the peripheral benzodiazepine receptor with [11C] DAA1106
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DOI：
10.1038/sj.jcbfm.9600325
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发表时间：
2007-01-01
影响因子：
6.3
通讯作者：
Suzuki, Kazutoshi
中科院分区：
文献类型：
--
作者：
Ikoma, Yoko;Yasuno, Fumihiko;Suzuki, Kazutoshi
[(11)C] DAA1106 是外周苯二氮卓受体 (PBR) 的有效选择性配体，具有高亲和力。据报道，PBR的密度与脑损伤有关，因此需要一种可靠的示踪剂方法来评估PBR。我们评估了模拟数据和人脑数据中 [(11)C] DAA1106 结合的量化方法。在仿真研究中，评估了非线性最小二乘法（NLS）、图解分析（GA）和多线性分析（MA）估计参数的可靠性。在 GA 中，估计分布体积 (DV) 的变化很小。然而，随着噪声的增加，DV 被低估。 MA 中的偏差较小，估计 DV 的变化比 GA 中的大。在 NLS 中，虽然变异比 GA 中大，但在感兴趣区域分析中变异足够小，不仅可以估计 DV，还可以估计从 k(3)/k(4) 确定的没有任何约束的结合电位 (BP)。当k(3)或k(4)变小时，用NLS估计的BP的变化变大。在对正常志愿者的人体研究中，在几个大脑区域上绘制了感兴趣区域，通过 NLS 计算 BP，并且还通过 NLS、GA 和 MA 估计 DV。因此，用每种方法估计的 DV 具有良好的相关性。然而，由于个体间 K(1)/k(2) 存在差异，BP 与 NLS 以及 DV 与 NLS、GA 和 MA 之间没有相关性。总之，使用二组织室模型的 NLS 估计血压最为可靠。
[(11)C] DAA1106 is a potent and selective ligand for the peripheral benzodiazepine receptor (PBR) with high affinity. It has been reported that the density of PBR is related to brain damage, so a reliable tracer method for the evaluation of PBR would be of use. We evaluated a quantification method of [(11)C] DAA1106 binding in simulated data and human brain data. In the simulation study, the reliability of parameters estimated from the nonlinear least-squares (NLS) method, graphical analysis (GA), and multilinear analysis (MA) was evaluated. In GA, variation of the estimated distribution volume (DV) was small. However, DV was underestimated as noise increased. In MA, bias was smaller, and variation of the estimated DV was larger than in GA. In NLS, although variation was larger than in GA, it was small enough in regions of interest analysis, and not only DV but also binding potential (BP), determined from the k(3)/k(4) without any constraint, could be estimated. The variation of BP estimated with NLS became larger as k(3) or k(4) became smaller. In human studies with normal volunteers, regions of interest were drawn on several brain regions, BP was calculated by NLS, and DV was also estimated by NLS, GA, and MA. As a result, DVs estimated with each method were well correlated. However, there was no correlation between BP with NLS and DV with NLS, GA, and MA, because of the variation of K(1)/k(2) between individuals. In conclusion, BP is estimated most reliably by NLS with the two-tissue compartment model.