Imaging of Central Dopamine Discharge using Positron Emission Tomography

这项研究的目的是建立一种简化的非侵入性方法，利用正电子发射断层扫描来评估中枢多巴胺的释放。单次注射多巴胺(DA)系统的方法在硅胶和活体上都得到了验证。比较了[^&lt；11&gt；C]标记的雷氯普利和奈莫那必利在纹状体和参比组织(小脑/枕叶皮质)中的药代动力学。采用Lammertsma和Gunn实现的简化参考组织模型对组织数据进行模拟和分析。模拟研究表明，通过干预改变受体部位的结合电位，可以改变与DA受体的配体结合。连续双45分钟扫描被选为DA激活的实用方案。奈莫那必利被选为测试配体的原因如下：(1)相对较高的非特异性结合，有利于向受体持续供应游离配体；(2)与D2样受体的亲和力相对较高。因此，在扫描的后期，纹状体中的奈莫那必利放射性达到准平衡，这一状态与Carson等人实现的连续配基注射方法非常相似。在人体研究中，使用温和的10赫兹光驱动作为DA刺激，持续30分钟。对奈莫那必利组织放射性的动力学分析显示，实际组织放射性与根据50分钟的动力学数据计算的预测组织曲线有明显差异。尽管在没有激活的对照数据中发现了这种差异，但激活和没有激活之间的差异是显著的(有激活和没有激活的组织数据的预测和实际组织数据之间的平均分数差分别为6.0%±5.6%和2.1%±4.9%(t=3.423，p&lt；0.001)。

The aim of this study is to establish a simplified non-invasive method to assess central dopamine release using positron emission tomography. Single bolus injection method with activations of dopamine (DA) systems was tested both in silico and in vivo. [^<11>C] labeled raclopride and nemonapride were compared in their kinetics in the striatum and in reference tissues (cerebellum/occipital cortex). The simplified reference tissue model implemented by Lammertsma and Gunn was employed for the simulation and analysis of tissue data. Simulation studies revealed that ligand binding to DA receptors could be changed after intervention that alters binding potentials of receptor sites. Continuous dual 45 minutes scans was chosen as a practical protocol of DA activations. [^<11>C]nemonapride was selected for the test ligand because of the following reasons; (1)relatively high non-specific bindings which is beneficial for continuous supply of free ligands to the receptors, (2)relatively high affinity to the D2-like receptors. Consequently, nemonapride radioactivity in the striatum reaches quasi-equilibrium in the late phase of scans, the state closely similar with continuous ligand injection method implemented by Carson et al. For human studies mild 10 Hz photo driving was used as a DA stimulus for 30 minutes. Kinetic analyses of nemonapride tissue radioactivity revealed clear discrepancies of actual tissue radioactivity from predicted tissue curves calculated from the kinetic data taken up to 50 minutes. Although this discrepancies were found in the control data without activation, the difference was significant between with activation and without activation (average fractional difference between the predicted and actual tissue data were 6.0±5.6% and 2.1±4.9%.for with activation and without activation respectively (t = 3.423, p<0.001).