Regional heterogeneity of 5-HT1A receptors in human cerebellum as assessed by positron emission tomography
Regional heterogeneity of 5-HT1A receptors in human cerebellum as assessed by positron emission tomography
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DOI：
10.1038/sj.jcbfm.9600072
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发表时间：
2005-07-01
影响因子：
6.3
通讯作者：
Mann, JJ
中科院分区：
文献类型：
--
作者：
Parsey, RV;Arango, V;Mann, JJ
脑成像中使用的两个测量方法是结合电位 (BP) 和特异性与非特异性平衡分配系数 (V-3")。使用 5-HT1A 配体 [C-11]WAY-100635 测定的 V-3" 对参考区域中配体的游离和非特异性结合的变化敏感 (V,)。与男性相比，健康女性志愿者的 5-HT1A BP 较高，但 V-3" 没有，因为女性 V-2 较高。虽然这一观察结果可能有多种解释，但我们假设女性小脑中有更多 5-HT1A 受体。我们探索小脑以定义一个更准确代表游离和非特异性结合的亚区域，从而有可能允许使用 V-3"。使用 [H-3]WAY-100635 对人脑进行定量放射自显影图，发现小脑亚区域缺乏 5-HT1A 受体。使用 [C-11]WAY-100635 对 12 名健康女性和 13 名健康男性体内 5-HT1A 受体进行了评估。每个受试者都有代谢物校正的动脉输入功能。放射自显影图显示小脑白质 (CW) 中 5-HT1A 受体浓度最低，小脑蚓部 (CV) 中浓度最高。 CW 分布容积 (V-T) 低于 CV。小脑白质可以通过单组织区室模型充分建模，而对 CV 或总小脑 (CT) 进行建模则需要两组织模型。与男性相比，女性的 CW V-T 较高，表明 V-2 存在差异。 CW 的使用提高了皮质区域 BP 的可识别性和时间稳定性。小脑白质可能是未来使用 [C-11]WAY-100635 进行 5-HT1A 研究的更好参考区域。以CW作为参考区域，V-3"不能用于检测男性和女性之间5-HT1A受体的差异，这表明需要动脉输入功能来确定血压。
Two measures used in brain imaging are binding potential (BP) and the specific to nonspecific equilibrium partition coefficient (V-3"). V-3" determined using the 5-HT1A ligand [C-11]WAY-100635 is sensitive to changes in the free and nonspecific binding of the ligand in the reference region (V,). Healthy female volunteers have higher 5-HT1A BP but not V-3" compared with men, because V-2 is higher in women. While there could be several explanations for this observation, we hypothesized that women have more 5-HT1A receptors in the cerebellum. We explore the cerebellum to define a subregion that more accurately represents the free and nonspecific binding, potentially allowing the use of V-3". A quantitative autoradiogram in human brain using [H-3]WAY-100635 identified a cerebellar subregion devoid of 5-HT1A receptors. In vivo 5-HT1A receptors were evaluated using [C-11]WAY-100635 in 12 healthy women and 13 healthy men. Each subject had a metabolite-corrected arterial input function. The autoradiogram demonstrates the lowest concentration of 5-HT1A receptors in the cerebellar white matter (CW) and highest concentration in the cerebellar vermis (CV). The CW volume of distribution (V-T) is lower than CV. Cerebellar white matter is adequately modeled by a one-tissue compartmental model, while a two-tissue model is necessary to model CV or the total cerebellum (CT). Women have a higher CW V-T compared with men, suggesting a difference in V-2. Use of CW improves identifiability and time stability of BP in cortical regions. Cerebellar white matter might be a better reference region for use in future 5-HT1A studies using [C-11]WAY-100635. With CW as a reference region, V-3" cannot be used to detect differences in 5-HT1A receptors between men and women, suggesting the need for arterial input functions to determine BP.