Positron emission tomography displacement sensitivity: predicting binding potential change for positron emission tomography tracers based on their kinetic characteristics
Positron emission tomography displacement sensitivity: predicting binding potential change for positron emission tomography tracers based on their kinetic characteristics
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DOI：
10.1038/sj.jcbfm.9600359
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发表时间：
2007-03-01
影响因子：
6.3
通讯作者：
Yoder, Karmen K.
中科院分区：
文献类型：
--
作者：
Morris, Evan D.;Yoder, Karmen K.
正电子发射断层扫描（PET）作为突触神经递质水平波动的非侵入性检测方法，引起了人们极大的兴趣，但关于这种任务的示踪剂的最佳选择仍然存在问题。提出了一种数学方法，用于预测任何PET示踪剂作为内源性竞争剂浓度变化的检测器的效用，通过示踪剂的位移（a. K. a.将所述第一它对竞争的“脆弱性”）。该方法是基于早期的理论工作的恩德雷斯和卡森和作者。示踪剂特异性预测因子PET位移灵敏度（PDS）是在多巴胺（DA）短暂升高的情况下，根据多巴胺能放射性示踪剂摄取和保留的房室模型模拟计算的。PDS预测由于内源性竞争物的结合而引起的受体占有率给定变化的结合电位（DBP）变化。使用来自文献的示踪剂动力学参数的估计进行模拟。对于D-2/D-3示踪剂，计算的PDS指数表明对DA位移敏感性的等级顺序如下：雷氯必利（最高敏感性），其次是fallypride、FESP、FLB、NMSP和Escherichia pride（最低）。虽然PDS考虑了示踪剂在结合位点的亲和常数，但其预测值不能通过单一平衡常数或模型的任何一个速率常数来匹配。DBP值来自已发表的研究，这些研究采用了安非他明和D-2/D-3示踪剂的可比置换范例。这些值与PDS预测的位移敏感性等级顺序非常一致。
There is great interest in positron emission tomography ( PET) as a noninvasive assay of fluctuations in synaptic neurotransmitter levels, but questions remain regarding the optimal choice of tracer for such a task. A mathematical method is proposed for predicting the utility of any PET tracer as a detector of changes in the concentration of an endogenous competitor via displacement of the tracer ( a. k. a., its ` vulnerability' to competition). The method is based on earlier theoretical work by Endres and Carson and by the authors. A tracer- specific predictor, the PET Displacement Sensitivity ( PDS), is calculated from compartmental model simulations of the uptake and retention of dopaminergic radiotracers in the presence of transient elevations of dopamine ( DA). The PDS predicts the change in binding potential ( DBP) for a given change in receptor occupancy because of binding by the endogenous competitor. Simulations were performed using estimates of tracer kinetic parameters derived from the literature. For D-2/D-3 tracers, the calculated PDS indices suggest a rank order for sensitivity to displacement by DA as follows: raclopride ( highest sensitivity), followed by fallypride, FESP, FLB, NMSP, and epidepride ( lowest). Although the PDS takes into account the affinity constant for the tracer at the binding site, its predictive value cannot be matched by either a single equilibrium constant, or by any one rate constant of the model. Values for DBP have been derived from published studies that employed comparable displacement paradigms with amphetamine and a D-2/D-3 tracer. The values are in good agreement with the PDS- predicted rank order of sensitivity to displacement.