Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Region Stockholm, Stockholm SE -171 76, Sweden.
Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Region Stockholm, Stockholm SE -171 76, Sweden.
Neuroimage. 2021 Feb 1;226:117523. doi: 10.1016/j.neuroimage.2020.117523. Epub 2020 Nov 2.
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 [C]FLB 457 for D2-R quantification in extrastriatal brain regions. However, this radioligand is not available at most research centers. Instead, the medium affinity radioligand [C]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 [C]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 [C]raclopride and [C]FLB 457 to assess the correlation in binding potential (BP) in extrastriatal brain regions. BP was quantified using the simplified reference tissue model with cerebellum as reference region. The rank order of mean regional BP 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 [C]raclopride and [C]FLB 457 BP extrastriatally (Pearson's R: 0.30-0.56), in contrast to very strong correlations between repeated [C]FLB 457 measurements (Pearson's R: 0.82-0.98). In comparison, correlations between repeated [C]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 [C]raclopride in extrastriatal brain regions, and further strengthen the recommendation that extrastriatal D2-R measures obtained with [C]raclopride should be interpreted with caution.
纹状体外脑区的多巴胺 D2 受体（D2-R）是广泛的精神和神经疾病研究的热点。药理学竞争研究和重复测试实验表明，正电子发射断层扫描（PET）放射性配体 [C]FLB 457 对纹状体外脑区 D2-R 定量具有很高的有效性和可靠性。然而，这种放射性配体在大多数研究中心都无法获得。相反，已广泛验证用于高浓度纹状体 D2-R 定量的中等亲和力放射性配体 [C]raclopride 也已应用于纹状体外 D2-R 的研究。最近，在一项使用喹硫平进行的药理学竞争研究中，观察到 [C]raclopride 在纹状体外区域的占有率较低，这对这种方法的有效性提出了质疑。在这里，我们利用一组 16 名健康对照者的数据集，这些对照者同时接受了 [C]raclopride 和 [C]FLB 457 的检查，以评估纹状体外脑区结合潜能（BP）的相关性。使用小脑作为参照区的简化参照组织模型来定量 BP。两种放射性配体的平均区域 BP 值的等级顺序相似，与死后和使用 PET 的先前报道的数据一致。尽管如此，在纹状体外，[C]raclopride 和 [C]FLB 457 BP 之间观察到弱至中度的个体内相关性（Pearson's R：0.30-0.56），而在反复测量 [C]FLB 457 时则存在非常强的相关性（Pearson's R：0.82-0.98）。相比之下，重复测量 [C]raclopride 之间的相关性较低至中等（Pearson's R：0.28-0.75）。这些结果可能与 [C]raclopride 在纹状体外脑区的信噪比低有关，进一步加强了建议，即使用 [C]raclopride 获得的纹状体外 D2-R 测量值应谨慎解释。
