Dopamine D2 receptors (D2-R) in extrastriatal brain regions are of high interest for research in a wide range of psychiatric and neurologic disorders. Pharmacological competition studies and test-retest experiments have shown high validity and reliability of the positron emission tomography (PET) radioligand [11C]FLB 457 for D2-R quantification in extrastriatal brain regions. However, this radioligand is not available at most research centres. Instead, the medium affinity radioligand [11C]raclopride, which has been extensively validated for quantification of D2-R in the high-density region striatum, has been applied also in studies on extrastriatal D2-R. Recently, the validity of this approach has been questioned by observations of low occupancy of [11C]raclopride in extrastriatal regions in a pharmacological competition study with quetiapine. Here, we utilise a data set of 16 healthy control subjects examined with both [11C]raclopride and [11C]FLB 457 to assess the correlation in binding potential (BPND) in extrastriatal brain regions. BPND was quantified using the simplified reference tissue model with cerebellum as reference region. The rank order of mean regional BPND values were similar for both radioligands, and corresponded to previously reported data, both post-mortem and using PET. Nevertheless, weak to moderate within-subject correlations were observed between [11C]raclopride and [11C]FLB 457 BPND extrastriatally (Pearson's R: 0.30 - 0.56), in contrast to very strong correlations between repeated [11C]FLB 457 measurements (Pearson's R: 0.82 - 0.98). In comparison, correlations between repeated [11C]raclopride measurements were low to moderate (Pearson's R: 0.28 - 0.75). These results are likely related to low signal to noise ratio of [11C]raclopride in extrastriatal brain regions, and further strengthen the recommendation that extrastriatal D2-R measures obtained with [11C]raclopride should be interpreted with caution.

中文翻译：

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[11C]raclopride 结合在纹状体外脑区的低收敛效度：与 [11C]FLB 457 受试者内相关性的 PET 研究

纹状体外脑区的多巴胺 D2 受体 (D2-R) 对广泛的精神和神经系统疾病的研究具有很高的兴趣。药理学竞争研究和重测实验表明，正电子发射断层扫描 (PET) 放射性配体 [11C] FLB 457 在纹状体外脑区进行 D2-R 量化具有很高的有效性和可靠性。但是，大多数研究中心都没有这种放射性配体。相反，中等亲和力放射性配体 [11C] raclopride 已被广泛验证用于高密度区域纹状体中 D2-R 的定量，也已应用于纹状体外 D2-R 的研究。最近，在与喹硫平进行的药理学竞争研究中，观察到 [11C] raclopride 在纹状体外区域的低占有率，对这种方法的有效性提出了质疑。在这里，我们利用用 [11C] raclopride 和 [11C]FLB 457 检查的 16 名健康对照受试者的数据集来评估纹状体外脑区结合电位 (BPND) 的相关性。使用以小脑作为参考区域的简化参考组织模型对 BPND 进行量化。两种放射性配体的平均区域 BPND 值的等级顺序相似，并且对应于先前报告的数据，无论是验尸还是使用 PET。尽管如此，在 [11C] raclopride 和 [11C]FLB 457 BPND 纹外（Pearson's R：0.30 - 0.56）之间观察到弱到中等的受试者内相关性，与重复 [11C] FLB 457 测量（Pearson's R : 0.82 - 0.98)。相比之下，重复 [11C] raclopride 测量值之间的相关性为低到中等（Pearson's R：0。28 - 0.75)。这些结果可能与 [11C]raclopride 在纹状体外脑区的低信噪比有关，并进一步加强了使用 [11C]raclopride 获得的纹外 D2-R 测量值应谨慎解释的建议。