Comparison of two compartmental models for describing receptor ligand kinetics and receptor availability in multiple injection PET studies.
Comparison of two compartmental models for describing receptor ligand kinetics and receptor availability in multiple injection PET studies.
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多次注射 PET 研究中描述受体配体动力学和受体可用性的两种房室模型的比较。
DOI：
10.1097/00004647-199609000-00009
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Fischman,AJ
中科院分区：
文献类型：
--
作者：
Morris,ED;Alpert,NM;Fischman,AJ
受体配体和PET研究的目标是表征体内系统，该系统测量配体-受体复合物的结合和解离速率以及可用结合位点的密度。有人认为，放射性配体的多次注射研究比单次注射研究更有可能确定模型参数。通常，至少一次后期注射处于低比活度（SA），使得正电子发射断层扫描（PET）曲线的一部分反映配体解离。然而，低SA注射和伴随的受体可用性的降低可能违反示踪剂动力学假设，即示踪剂可能不再与总（标记和未标记）配体处于稳定状态。组织反应变得严重依赖于总配体的剂量，并且需要对组织中的冷配体进行准确描述以正确地对系统进行建模。两种替代模型已被应用到受体建模问题，这减少到描述随时间变化的可用受体位点的数量。第一个仅包含热配体的隔室，“仅热”（HO），但间接占冷配体通过SA在受体位点的作用。第二个规定了热配体和冷配体的单独隔室，即“热配体和冷配体”（HC），从而明确计算出受体的可用数量。我们检查了这些模型，并对比了它们预测PET活性、受体可用性和每个组织隔室中SA的能力。对于多次注射研究，模型一致地预测不同的PET活性-特别是在第三次注射后。只有在非常高的速率常数下，多次进样的模型才相同。在一种情况下，模拟PET曲线非常相似，但在受体可用性的预测中出现了差异。HO模型预测了受体位点可用性的非生理变化，并在测试数据的B′ max估计中引入了30-60%的误差。因此，我们强烈建议在多次注射PET研究的所有分析中使用HC模型。
The goal of research with receptor ligands and PET is the characterization of an in vivo system that measures rates of association and dissociation of a ligand-receptor complex and the density of available binding sites. It has been suggested that multiple injection studies of radioactive ligand are more likely to identify model parameters than are single injection studies. Typically, at least one of the late injections is at a low specific activity (SA), so that part of the positron emission tomography (PET) curve reflects ligand dissociation. Low SA injections and the attendant reductions in receptor availability, however, may violate tracer kinetic assumptions, namely, tracer may no longer be in steady state with the total (labeled and unlabeled) ligand. Tissue response becomes critically dependent on the dose of total ligand, and an accurate description of the cold ligand in the tissue is needed to properly model the system. Two alternative models have been applied to the receptor modeling problem, which reduces to describing the time-varying number of available receptor sites. The first contains only compartments for the hot ligand, ‘hot only’ (HO), but indirectly accounts for the action of cold ligand at receptor sites via SA. The second stipulates separate compartments for the hot and cold ligands, ‘hot and cold’ (HC), thus explicitly calculating available number of receptors. We examined these models and contrasted their abilities to predict PET activity, receptor availability, and SA in each tissue compartment. For multiple injection studies, the models consistently predicted different PET activities—especially following the third injection. Only for very high rate constants were the models identical for multiple injections. In one case, simulated PET curves were quite similar, but discrepancies appeared in predictions of receptor availability. The HO model predicted nonphysiological changes in the availability of receptor sites and introduced errors of 30–60% into estimates of B′maxfor test data. We, therefore, strongly recommend the use of the HC model for all analyses of multiple injection PET studies.
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