Parsey R V, Slifstein M, Hwang D R, Abi-Dargham A, Simpson N, Mawlawi O, Guo N N, Van Heertum R, Mann J J, Laruelle M
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA.
J Cereb Blood Flow Metab. 2000 Jul;20(7):1111-33. doi: 10.1097/00004647-200007000-00011.
Serotonin 5-HT(1A) receptors are implicated in the pathophysiology of neuropsychiatric conditions. The goal of this study was to evaluate methods to derive 5-HT(1A) receptor parameters in the human brain with positron emission tomography (PET) and [carbonyl-(11)C]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 (k3/k4). 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 k3/k4. 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 k3/k4. All methods provided estimates of regional 5-HT(1A) receptor parameters that were highly correlated. Results were consistent with the known distribution of 5-HT(1A) receptors in the human brain. Compared with kinetic BP, graphical analysis slightly underestimated BP, and this phenomenon was mostly apparent in small size-high noise regions. Compared with kinetic k3/k4, the reference tissue method underestimated k3/k4 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 k3/k4 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.
血清素5-HT(1A)受体与神经精神疾病的病理生理学有关。本研究的目的是评估用正电子发射断层扫描(PET)和[羰基-(11)C]WAY 100635在人脑中得出5-HT(1A)受体参数的方法。对5名健康志愿者进行了两次研究。使用三种分析方法得出结合势(BP)以及特异性与非特异性平衡分配系数(k3/k4)。两种方法，即基于三室模型的动力学分析和图形分析，使用动脉血浆时间-活度曲线作为输入函数来得出BP和k3/k4。第三种方法，简化参考组织模型(SRTM)，从参考区域小脑的摄取数据得出输入函数，并且只提供k3/k4。所有方法得出的区域5-HT(1A)受体参数估计值高度相关。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，图形分析略微低估了BP，并且这种现象在小尺寸高噪声区域最为明显。与动力学k3/k4相比，参考组织方法低估了k3/k4，并且这种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得出BP的可靠性很高，组内相关系数(ICC)分别为0.84±0.14(15个区域的平均值±标准差)和0.84±0.19。相比之下，k3/k4的可靠性较低，动力学、图形和参考组织方法的ICC分别为0.53±0.28、0.47±0.28和0.55±0.29。总之，使用动脉血浆输入函数通过动力学分析得出BP似乎是首选方法，因为其重测再现性更高、对实验噪声的敏感性更低且无偏差。
