Imaging of Central Dopamine Discharge using Positron Emission Tomography

本研究的目的是建立一个简单的非侵入性的方法来评估中枢多巴胺释放使用正电子发射断层扫描。在计算机模拟和体内测试了具有多巴胺（DA）系统激活的单次推注方法。比较了[^<11>C]标记的雷氯必利和奈莫那必利在纹状体和参照组织（小脑/枕叶皮质）中的动力学。采用Lammertsma和古恩实现的简化参考组织模型进行组织数据的模拟和分析。模拟研究表明，DA受体的配体结合可以改变干预后，改变受体位点的结合电位。选择连续双45分钟扫描作为DA激活的实用方案。由于<11>以下原因，选择[13 C]奈莫那必利作为测试配体：（1）相对高的非特异性结合，这有利于向受体连续供应游离配体，（2）相对高的对D2样受体的亲和力。因此，纹状体中的奈莫那必利放射性在扫描的后期达到准平衡，该状态与卡森等人实施的连续配体注射方法非常相似。对于人体研究，温和的10 Hz光驱动用作DA刺激30分钟。奈莫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分钟内的动力学数据计算的预测组织曲线存在明显差异。虽然在没有激活的对照数据中发现了这种差异，但是在有激活和没有激活之间的差异是显著的（对于有激活和没有激活，预测和实际组织数据之间的平均分数差异分别为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).