Validation and reproducibility of measurement of 5-HT1A receptor parameters with [carbonyl-11C]WAY-100635 in humans:: Comparison of arterial and reference tissue input functions
Validation and reproducibility of measurement of 5-HT1A receptor parameters with [carbonyl-11C]WAY-100635 in humans:: Comparison of arterial and reference tissue input functions
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DOI：
10.1097/00004647-200007000-00011
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发表时间：
2000-07-01
影响因子：
6.3
通讯作者：
Laruelle, M
中科院分区：
文献类型：
--
作者：
Parsey, RV;Slifstein, M;Laruelle, M
5-羟色胺5-HT 1A受体与神经精神疾病的病理生理学有关。本研究的目的是评价方法，以获得5-HT 1A受体参数在人脑正电子发射断层扫描（PET）和[carborzyl-C-11]WAY 100635。对5名健康志愿者进行了两次研究。使用三种分析方法推导结合势（BP）和特异性与非特异性平衡分配系数（k（3）/k（4））。基于三室模型的动力学分析和图形分析这两种方法使用动脉血浆时间-活性曲线作为输入函数来推导BP和k（3）/k（4）。第三种方法是简化的参考组织模型（SRTM），从参考区域小脑的摄取数据导出输入函数，仅提供k（3）/k（4）。所有的方法提供了高度相关的区域5-HT 1A受体参数的估计。结果与5-HT 1A受体在人脑中的已知分布一致。与动力学BP相比，图形分析略低估了BP，这种现象在小尺寸高噪声区域最为明显。与动力学k（3）/k（4）相比，参考组织法低估了k，flc，并且低估主要在受体密度高的区域明显。通过动力学和图形分析推导出的BP高度可靠，组内相关系数（ICC）分别为0.84 +/- 0.14（15个区域的平均值+/- SD）和0.84 +/- 0.19。相比之下，k（3）/k（4）的可靠性较低，动力学法、图解法和参考组织法的ICC分别为0.53 +/- 0.28、0.47 +/- 0.28和0.55 +/- 0.29。总之，推导出的BP动力学分析使用动脉血浆输入功能出现的方法的选择，因为其较高的重测重现性，较低的脆弱性实验噪音，和没有偏见。
Serotonin 5-HT1A receptors are implicated in the pathophysiology of neuropsychiatric conditions. The goal of this study was to evaluate methods to derive 5-HT1A receptor parameters in the human brain with positron emission tomography (PET) and [carborzyl-C-11]WAY 100635. Five healthy volunteer subjects were studied twice. Three methods of analysis were used to derive the binding potential (BP), and the specific to nonspecific equilibrium partition coefficient (k(3)/k(4)). Two methods, kinetic analysis based on a three compartment model and graphical analysis, used the arterial plasma time-activity curves as the input function to derive BP and k(3)/k(4). A third method, the simplified reference tissue model (SRTM), derived the input function from uptake data of a region of reference, the cerebellum, and provided only k(3)/k(4). All methods provided estimates of regional 5-HT1A receptor parameters that were highly correlated. Results were consistent with the known distribution of 5-HT1A receptors in the human brain. Compared with kinetic BP, graphical analysis slightly underestimated BP, and this phenomenon was mostly apparent in mall size-high noise regions. Compared with kinetic k(3)/k(4), the reference tissue method underestimated k,flc, and the underestimation was apparent primarily in regions with high receptor density. Derivation of BP by both kinetic and graphical analysis was highly reliable, with an intraclass correlation coefficient (ICC) of 0.84 +/- 0.14 (mean +/- SD of 15 regions) and 0.84 +/- 0.19, respectively. In contrast, the reliability of k(3)/k(4) was lower, with ICC of 0.53 +/- 0.28, 0.47 +/- 0.28, and 0.55 +/- 0.29 for kinetic, graphical, and reference tissue methods, respectively. In conclusion, derivation of BP by kinetic analysis using the arterial plasma input function appeared as the method of choice because of its higher test-retest reproducibility, lower vulnerability to experimental noise, and absence of bias.