Development of medications selective for dopamine D2 or D3 receptors is an active area of research in numerous neuropsychiatric disorders including addiction and Parkinson's disease. The positron emission tomography (PET) radiotracer [11C]-(+)-PHNO, an agonist that binds with high affinity to both D2 and D3 receptors, has been used to estimate relative receptor subtype occupancy by drugs based on a priori knowledge of regional variation in the expression of D2 and D3 receptors. The objective of this work was to use a data-driven independent component analysis (ICA) of receptor blocking scans to separate D2-and D3-related signal in [11C]-(+)-PHNO binding data in order to improve the precision of subtype specific measurements of binding and occupancy. Eight healthy volunteers underwent [11C]-(+)-PHNO PET scans at baseline and at two time points following administration of the D3-preferring antagonist ABT-728 (150-1000 mg). Parametric binding potential (BPND) images were analyzed as four-dimensional image series using ICA to extract two independent sources of variation in [11C]-(+)-PHNO BPND. Spatial source maps for each component were consistent with respective regional patterns of D2-and D3-related binding. ICA-derived occupancy estimates from each component were similar to D2-and D3-specific occupancy estimated from a region-based approach (intraclass correlation coefficients > 0.95). ICA-derived estimates of D3 receptor occupancy improved quality of fit to a single site binding model. Furthermore, ICA-derived estimates of the regional fraction of [11C]-(+)-PHNO binding related to D3 receptors was generated for each subject and values showed good agreement with region-based model estimates and prior literature values. In summary, ICA successfully separated D2-and D3-related components of the [11C]-(+)-PHNO binding signal, establishing this approach as a powerful data-driven method to quantify distinct biological features from PET data composed of mixed data sources.

中文翻译：

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分离 [11C]-(+)-PHNO 结合潜力的多巴胺 D2 和 D3 受体来源：竞争性结合的独立成分分析

开发针对多巴胺 D2 或 D3 受体的选择性药物是许多神经精神疾病（包括成瘾和帕金森病）的活跃研究领域。正电子发射断层扫描 (PET) 放射性示踪剂 [11C]-(+)-PHNO，一种以高亲和力结合 D2 和 D3 受体的激动剂，已被用于基于区域的先验知识估计药物的相对受体亚型占有率。 D2 和 D3 受体表达的变化。这项工作的目的是使用受体阻断扫描的数据驱动独立成分分析 (ICA) 来分离 [11C]-(+)-PHNO 结合数据中的 D2 和 D3 相关信号，以提高结合和占用的亚型特异性测量。八名健康志愿者在基线和给药 D3 首选拮抗剂 ABT-728（150-1000 mg）后的两个时间点接受了 [11C]-(+)-PHNO PET 扫描。参数结合电位 (BPND) 图像被分析为四维图像系列，使用 ICA 提取 [11C]-(+)-PHNO BPND 中两个独立的变异来源。每个组件的空间源图与 D2 和 D3 相关绑定的各自区域模式一致。来自每个组件的 ICA 派生占用率估计类似于从基于区域的方法估计的 D2 和 D3 特定占用率（类内相关系数 > 0.95）。ICA 衍生的 D3 受体占有率估计提高了对单位点结合模型的拟合质量。此外，为每个受试者生成了与 D3 受体相关的 [11C]-(+)-PHNO 结合的区域分数的 ICA 估计值，并且值与基于区域的模型估计值和先前文献值显示出良好的一致性。总之，ICA 成功地分离了 [11C]-(+)-PHNO 结合信号的 D2 和 D3 相关成分，将此方法确立为一种强大的数据驱动方法，可从由混合数据源组成的 PET 数据中量化不同的生物特征.