Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm County Council, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
Neurobiology Research Unit, Copenhagen University Hospital, Copenhagen, Denmark.
Neuroimage. 2019 Nov 15;202:116143. doi: 10.1016/j.neuroimage.2019.116143. Epub 2019 Aug 29.
[C]raclopride is a well established PET tracer for the quantification of dopamine 2/3 receptors (DR) in the striatum. Outside of the striatum the receptor density is up to two orders of magnitude lower. In contrast to striatal binding, the characteristics of extrastriatal [C]raclopride binding quantification has not been thoroughly described. Still, binding data for e.g., neocortex is frequently reported in the scientific literature. Here we evaluate the validity and reliability of extrastriatal [C]raclopride binding quantification. Two sets of healthy control subjects were examined with HRRT and [C]raclopride: (i) To assess the validity of extrastriatal [C]raclopride binding estimates, eleven subjects were examined at baseline and after dosing with quetiapine, a DR antagonist. (ii) To assess test-retest repeatability, nine subjects were examined twice. Non displaceable binding potential (BP) was quantified using the simplified reference tissue model with cerebellum as reference. Quetiapine dosing was associated with decrease in [C]raclopride BP in temporal cortex (18 ± 17% occupancy) and thalamus (20 ± 17%), but not in frontal cortex. Extrastriatal occupancy was lower than in putamen (51 ± 4%). The mean absolute variation was 4-7% in the striatal regions, 17% in thalamus, and 13-59% in cortical regions. Our data indicate that [C]raclopride PET, quantified using cerebellum as reference, is not a suitable tool to measure DR in extrastriatal regions.
[C]raclopride 是一种经过充分验证的 PET 示踪剂，可用于定量测量纹状体中的多巴胺 2/3 受体 (DR)。在纹状体之外，受体密度低至两个数量级。与纹状体内结合相比，外纹状体 [C]raclopride 结合的特征尚未得到彻底描述。尽管如此，例如，新皮层的结合数据在科学文献中经常被报道。在这里，我们评估了外纹状体 [C]raclopride 结合定量的有效性和可靠性。两组健康对照者接受了 HRRT 和 [C]raclopride 检查：(i) 为了评估外纹状体 [C]raclopride 结合估算的有效性，11 名受试者在基线时和接受 DR 拮抗剂喹硫平给药后接受了检查。(ii) 为了评估测试-重测重复性，9 名受试者接受了两次检查。使用简化的参考组织模型，以小脑作为参考，量化不可置换的结合潜力 (BP)。喹硫平给药与颞叶皮质 (18%±17%占有率) 和丘脑 (20%±17%) 中 [C]raclopride BP 的下降相关，但与额叶皮质无关。外纹状体占有率低于壳核 (51%±4%)。纹状体区域的平均绝对变异为 4-7%，丘脑为 17%，皮质区域为 13-59%。我们的数据表明，使用小脑作为参考进行量化的 [C]raclopride PET 不是测量外纹状体区域 DR 的合适工具。
