Endres C J, Carson R E
Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, Maryland 20892-1180, USA.
J Cereb Blood Flow Metab. 1998 Nov;18(11):1196-210. doi: 10.1097/00004647-199811000-00006.
To describe the effect of endogenous dopamine on [11C]raclopride binding, we previously extended the conventional receptor ligand model to include dynamic changes in neurotransmitter concentration. Here, we apply the extended model in simulations of neurotransmitter competition studies using either bolus or bolus-plus-infusion (B/I) tracer delivery. The purpose of this study was (1) to develop an interpretation of the measured change in tracer binding in terms of underlying neurotransmitter changes, and (2) to determine tracer characteristics that maximize sensitivity to neurotransmitter release. A wide range of kinetic parameters was tested based on existing reversible positron emission tomography tracers. In simulations of bolus studies, the percent reduction in distribution volume (deltaV) caused by a neurotransmitter pulse was calculated. For B/I simulations, equilibrium was assumed, and the maximum percent reduction in tissue concentration (deltaC) after neurotransmitter release was calculated. Both deltaV and deltaC were strongly correlated with the integral of the neurotransmitter pulse. The values of deltaV and deltaC were highly dependent on the kinetic properties of the tracer in tissue, and deltaV could be characterized in terms of the tissue free tracer concentration. The value of deltaV was typically maximized for binding potentials of approximately 3 to 10, with deltaC being maximized at binding potentials of approximately 1 to 2. Both measures increased with faster tissue-to-blood clearance of tracer and lower nonspecific binding. These simulations provide a guideline for interpreting the results of neurotransmitter release studies and for selecting radiotracers and experimental design.
为描述内源性多巴胺对[11C]雷氯必利结合的影响，我们之前扩展了传统的受体配体模型，以纳入神经递质浓度的动态变化。在此，我们将扩展模型应用于使用团注或团注加输注（B/I）示踪剂给药的神经递质竞争研究模拟中。本研究的目的是：（1）根据潜在的神经递质变化对示踪剂结合的测量变化进行解释；（2）确定对神经递质释放敏感性最大化的示踪剂特征。基于现有的可逆正电子发射断层显像示踪剂测试了广泛的动力学参数。在团注研究模拟中，计算了神经递质脉冲引起的分布容积减少百分比（deltaV）。对于B/I模拟，假设达到平衡，并计算神经递质释放后组织浓度的最大减少百分比（deltaC）。deltaV和deltaC均与神经递质脉冲的积分密切相关。deltaV和deltaC的值高度依赖于示踪剂在组织中的动力学特性，并且deltaV可以根据组织中游离示踪剂浓度来表征。对于约3至10的结合电位，deltaV的值通常最大，而对于约1至2的结合电位，deltaC最大。这两种测量值均随着示踪剂从组织到血液的清除速度加快和非特异性结合降低而增加。这些模拟为解释神经递质释放研究结果以及选择放射性示踪剂和实验设计提供了指导。
