COMPARTMENTAL ANALYSIS OF [C-11] FLUMAZENIL KINETICS FOR THE ESTIMATION OF LIGAND TRANSPORT RATE AND RECEPTOR DISTRIBUTION USING POSITRON EMISSION TOMOGRAPHY
COMPARTMENTAL ANALYSIS OF [C-11] FLUMAZENIL KINETICS FOR THE ESTIMATION OF LIGAND TRANSPORT RATE AND RECEPTOR DISTRIBUTION USING POSITRON EMISSION TOMOGRAPHY
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DOI：
10.1038/jcbfm.1991.130
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发表时间：
1991-09-01
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;HOLTHOFF, VA;KUHL, DE
[C-11]氟马西尼（[C-11]FMZ）是一种非亚型特异性中枢苯二氮卓类拮抗剂，本文利用区室分析对其体内动力学行为进行了表征，目的是为评估[C-11]FMZ与人脑苯二氮卓类受体（BZRs）的结合提供优化的数据采集方案和示踪动力学模型配置。所提出的方法很简单，只需要一个放射配体注入。通过60 ~ 90分钟的扫描序列获得18名正常志愿者的动态正电子发射断层扫描数据，并对模型配置进行分析，包括三室，四参数模型，三室，三参数模型，固定值为自由加非特异性结合；一个两室，两参数的模型。统计分析表明，四参数模型的拟合效果并不明显优于三参数模型。在低受体密度的区域，三参数配置的拟合优度比两参数配置的拟合优度有所提高，但在中等到高受体密度的区域则没有。因此，两室，两参数配置被发现足以描述[C-11]FMZ在人脑中的动力学行为，并且可以从20-30分钟的数据中获得模型参数的稳定估计。逐像素分析得到了运输速率（K1）和配体分布体积（DV）的功能图像，从而提供了配体递送和BZR结合的独立估计。
The in vivo kinetic behavior of [C-11]flumazenil ([C-11]FMZ), a non-subtype-specific central benzodiazepine antagonist, is characterized using compartmental analysis with the aim of producing an optimized data acquisition protocol and tracer kinetic model configuration for the assessment of [C-11]FMZ binding to benzodiazepine receptors (BZRs) in human brain. The approach presented is simple, requiring only a single radioligand injection. Dynamic positron emission tomography data were acquired on 18 normal volunteers using a 60- to 90-min sequence of scans and were analyzed with model configurations that included a three-compartment, four-parameter model, a three-compartment, three-parameter model, with a fixed value for free plus nonspecific binding; and a two-compartment, two-parameter model. Statistical analysis indicated that a four-parameter model did not yield significantly better fits than a three-parameter model. Goodness of fit was improved for three- versus two-parameter configurations in regions with low receptor density, but not in regions with moderate to high receptor density. Thus, a two-compartment, two-parameter configuration was found to adequately describe the kinetic behavior of [C-11]FMZ in human brain, with stable estimates of the model parameters obtainable from as little as 20-30 min of data. Pixel-by-pixel analysis yields functional images of transport rate (K1) and ligand distribution volume (DV"), and thus provides independent estimates of ligand delivery and BZR binding.