Imaging of Central Dopamine Discharge using Positron Emission Tomography

本研究的目的是建立一种简化的无创方法，利用正电子发射断层扫描来评估中枢多巴胺释放。采用单丸注射法对多巴胺（DA）系统进行了计算机和体内试验。[^<11>C]比较了标记的雷氯pride和奈莫那必利在纹状体和参考组织（小脑/枕皮质）中的动力学。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，干预可以改变配体与DA受体的结合，从而改变受体位点的结合电位。选择连续两次45分钟扫描作为DA激活的实用方案。[^<11>C]选择奈莫那必利作为测试配体，原因如下：(1)相对较高的非特异性结合，有利于持续向受体提供自由配体；(2)相对较高的与d2样受体的亲和力。因此，在扫描后期，纹状体中的奈莫那必利放射性达到准平衡，这种状态与Carson等人实现的连续配体注射方法非常相似。在人体研究中，轻度的10 Hz光驱动被用作30分钟的DA刺激。奈莫那必利组织放射性的动力学分析表明，根据50分钟的动力学数据计算的预测组织曲线与实际组织放射性有明显的差异。虽然在未激活的对照数据中发现了这种差异，但激活和未激活之间的差异是显著的（预测和实际组织数据之间的平均分数差异为6.0±5.6%和2.1±4.9%）。分别为活化和未活化（t = 3.423, p<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).