Rosa-Neto Pedro, Doudet Doris J, Cumming Paul
PET Centre, Aarhus University Hospitals, and Centre of Functionally Integrative Neuroscience (CFIN), Aarhus University, Aarhus, Denmark.
Neuroimage. 2004 Jul;22(3):1076-83. doi: 10.1016/j.neuroimage.2004.03.004.
The distributions of dopamine D1 and D2/3 binding sites in living brain have not been compared directly using positron emission tomography (PET). To map these binding sites, we first optimized methods for the assay of dopamine receptors in brain of Göttingen miniature pigs. The binding potentials (pB) of [11C]NNC 112 for dopamine D1 receptors and [11C]raclopride for dopamine D2/3 receptors were calculated in pig striatum volumes of interest using metabolite corrected arterial inputs or using cerebellum as a non-binding reference region. Depending upon the method for quantitation, the pB for [11C]NNC 112 was 1.2-5.1 in pig striatum, whereas the pB for [11C]raclopride was 1.0-1.8. We used the reference tissue method of Logan to calculate pB maps for the two tracers. The maps were co-registered to the common stereotaxic space for the pig brain and normalized to a global mean for pB in striatum; t-maps showed that dopamine D1 binding was relatively more abundant in the ventral-anterior striatum of the pig, while dopamine D2/3 binding was greater in the dorsal striatum. Similar comparisons were made for the pBs of [11C]Sch 23390 for dopamine D1 receptors and for [11C]raclopride in the brain of six rhesus monkeys. The magnitudes of pB for both binding sites in monkey brain were close to those in the pig. Consistent with the pig results, there were distinct gradients in the distributions of the two binding sites in monkey brain: D1 binding predominated in the ventral striatum, whereas D2/3 binding was relatively greater in the dorsal-posterior striatum. Gradients of dopamine receptor concentration within the striatum may be a general phenomenon of mammalian brain.
尚未使用正电子发射断层扫描（PET）直接比较活体大脑中多巴胺D1和D2/3结合位点的分布情况。为了绘制这些结合位点图谱，我们首先优化了 Göttingen 小型猪大脑中多巴胺受体的检测方法。使用代谢物校正的动脉输入或使用小脑作为非结合参考区域，在猪纹状体感兴趣体积中计算[11C]NNC 112对多巴胺D1受体的结合电位（pB）以及[11C]雷氯必利对多巴胺D2/3受体的结合电位。根据定量方法的不同，猪纹状体中[11C]NNC 112的pB为1.2 - 5.1，而[11C]雷氯必利的pB为1.0 - 1.8。我们使用 Logan 的参考组织方法计算两种示踪剂的pB图谱。这些图谱被共同配准到猪脑的通用立体定向空间，并归一化为纹状体中pB的全局平均值；t图谱显示，多巴胺D1结合在猪的腹侧前纹状体中相对更为丰富，而多巴胺D2/3结合在背侧纹状体中更强。对六只恒河猴大脑中多巴胺D1受体的[11C]Sch 23390和[11C]雷氯必利的pB进行了类似比较。猴脑中两个结合位点的pB大小与猪脑中的接近。与猪的结果一致，猴脑中两个结合位点的分布存在明显梯度：D1结合在腹侧纹状体中占主导，而D2/3结合在背侧后纹状体中相对更强。纹状体内多巴胺受体浓度的梯度可能是哺乳动物大脑的普遍现象。
