Quantitative analysis of dopaminergic synaptic function in human brain.

本研究旨在建立人脑多巴胺能突触功能的定量分析方法，包括SPECT显像的运动分析和大鼠新鲜脑片的基础实验，并进行基础和临床研究。I-123碘苯并呋喃(IBF)的连续动态SPECT成像与间歇性动脉采血允许获得多巴胺D2受体的结合潜力。除了隔室分析和简单的靶/非靶比方法外，我们还开发了一种新的图形方法，它提供了更可靠的受体结合参数。用I-123β-CIT的氟丙基类似物(FPCIT)进行多巴胺转运体显像。FPCIT具有比β-CIT更快的动力学优势，且测试和再测试脑SPECT扫描显示测量纹状体内分布体积的重复性很好，提示该示踪剂具有临床应用前景。我们还开发了一种名为动态正电子放射自显影技术(DPAT)的系统，用于对正电子标记的放射性配基的新鲜大鼠脑片进行连续成像。这种新方法可以评估几个小时内放射性的局部变化，并可用于监测葡萄糖代谢和与各种干预措施的受体结合，如低氧和药物效应。它将在理解放射性配体的动力学行为方面发挥重要作用。

The aim of this study was to establish the methods for the quantitative analysis of dopaminergic synaptic function in human brain, basic an clinical sdudies were performed with various approach, including the kinetc analysis of SPECT imaging and basic experiments using fresh brain slices of rats. Serial dynamic SPECT imaging of I-123 iodobenzofuran (IBF) with intermittent arterial blood sampling permits to obtain binding potential of dopamine D2 receptors. In addition to the compartment analysis and simple target to nontarget ratio approach, we have developed a new graphical method which provides more reliable parameters on receptor binding. Dopamine transporter imaging was performed with I-123 fluoropropyl analogue of beta-CIT (FPCIT). FPCIT has an advantage of faster kinetics than beta-CIT, and test anr re-test brain SPECT scans demonstrated an excellent reproducibility of measuring the distribution volume in the striatum, suggesting that this tracer is promising for the clinical use. We also developed a system called dynamic positron autoradiography technique (dPAT) for serial imaging of fresh brain slices of rats with positron labeled radioligands. This new method permits the assessment of regional changes of radioactivity for several hours, and can be used to monitor glucose metabolism and receptor binding with various interventions, such as hypoxia and drug effects. It will play an important role in understanding the kinetic behaviour of radioligands.