Narendran Rajesh, Frankle W Gordon, Mason N Scott, Rabiner Eugenii A, Gunn Roger N, Searle Graham E, Vora Shivangi, Litschge Maralee, Kendro Steve, Cooper Thomas B, Mathis Chester A, Laruelle Marc
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Synapse. 2009 Jun;63(6):447-61. doi: 10.1002/syn.20628.
The use of PET and SPECT endogenous competition binding techniques has contributed to the understanding of the role of dopamine in several neuropsychiatric disorders. An important limitation of these imaging studies is the fact that measurements of acute changes in synaptic dopamine have been restricted to the striatum. The ligands previously used, such as [(11)C]raclopride and [(123)I]IBZM, do not provide sufficient signal to noise ratio to quantify D(2) receptors in extrastriatal areas, such as cortex, where the concentration of D(2) receptors is much lower than in the striatum. Given the importance of cortical DA function in cognition, a method to measure cortical dopamine function in humans would be highly desirable. The goal of this study was to compare the ability of two high affinity DA D(2) radioligands [(11)C]FLB 457 and [(11)C]fallypride to measure amphetamine-induced changes in DA transmission in the human cortex. D(2) receptor availability was measured in the cortical regions of interest with PET in 12 healthy volunteers under control and postamphetamine conditions (0.5 mg kg(-1), oral), using both [(11)C]FLB 457 and [(11)C]fallypride (four scans per subjects). Kinetic modeling with an arterial input function was used to derive the binding potential (BP(ND)) in eight cortical regions. Under controlled conditions, [(11)C]FLB 457 BP(ND) was 30-70% higher compared with [(11)C]fallypride BP(ND) in cortical regions. Amphetamine induced DA release led to a significant decrease in [(11)C]FLB 457 BP(ND) in five out the eight cortical regions evaluated. In contrast, no significant decrease in [(11)C]fallypride BP(ND) was detected in cortex following amphetamine. The difference between [(11)C]FLB 457 and [(11)C]fallypride ability to detect changes in the cortical D(2) receptor availability following amphetamine is related to the higher signal to noise ratio provided by [(11)C]FLB 457. These findings suggest that [(11)C]FLB 457 is superior to [(11)C]fallypride for measurement of changes in cortical synaptic dopamine.
正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）内源性竞争结合技术的应用有助于理解多巴胺在几种神经精神疾病中的作用。这些成像研究的一个重要局限性在于，对突触多巴胺急性变化的测量一直局限于纹状体。先前使用的配体，如[（11）C]雷氯必利和[（123）I]碘苄酰胺，在纹状体以外的区域（如皮质），由于D（2）受体浓度远低于纹状体，无法提供足够的信噪比来定量D（2）受体。鉴于皮质多巴胺功能在认知中的重要性，一种测量人类皮质多巴胺功能的方法将非常受欢迎。本研究的目的是比较两种高亲和力多巴胺D（2）放射性配体[（11）C]FLB 457和[（11）C]法利哌啶测量苯丙胺诱导的人类皮质多巴胺传递变化的能力。在12名健康志愿者中，在对照和苯丙胺给药后（0.5mg/kg，口服）条件下，使用[（11）C]FLB 457和[（11）C]法利哌啶（每位受试者进行4次扫描），通过PET在感兴趣的皮质区域测量D（2）受体可用性。使用动脉输入函数的动力学模型来推导八个皮质区域的结合潜能（BP（ND））。在对照条件下，皮质区域中[（11）C]FLB 457的BP（ND）比[（11）C]法利哌啶的BP（ND）高30 - 70%。苯丙胺诱导的多巴胺释放导致在评估的八个皮质区域中的五个区域中，[（11）C]FLB 457的BP（ND）显著降低。相比之下，苯丙胺给药后，在皮质中未检测到[（11）C]法利哌啶的BP（ND）有显著降低。[（11）C]FLB 457和[（11）C]法利哌啶在检测苯丙胺后皮质D（2）受体可用性变化能力上的差异与[（11）C]FLB 457提供的更高信噪比有关。这些发现表明，在测量皮质突触多巴胺变化方面，[（11）C]FLB 457优于[（11）C]法利哌啶。
