EFFECTS OF BLOOD-FLOW ON [C-11] RACLOPRIDE BINDING IN THE BRAIN - MODEL SIMULATIONS AND KINETIC-ANALYSIS OF PET DATA
EFFECTS OF BLOOD-FLOW ON [C-11] RACLOPRIDE BINDING IN THE BRAIN - MODEL SIMULATIONS AND KINETIC-ANALYSIS OF PET DATA
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DOI：
10.1038/jcbfm.1994.132
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发表时间：
1994-11-01
影响因子：
6.3
通讯作者：
VITKUN, S
中科院分区：
文献类型：
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作者：
LOGAN, J;VOLKOW, ND;VITKUN, S
为了评估正电子发射断层扫描[C-11]雷氯必利（一种 D2 拮抗剂）研究中不同受体占据测量的稳定性，我们分析了正常志愿者中五项测试/再测试研究的数据，包括三室模型的个体模型参数、分布体积 (DV) 以及包含受体的感兴趣区域与不包含受体的区域的 DV 比率。在各个模型参数中发现了很大的变化，限制了它们作为受体系统变化指标的有用性。 DV 比率显示出最小的变化。个体差异反映在 DV 的受试者间变异大于受试者内变异。血流对这些测量的潜在影响通过实验和模拟研究得到了解决，使用三个模型明确地将血流纳入还包括受体-配体结合的区室模型中。只要模拟过程中血流保持恒定，所有模型都不会显示 DV 随血流变化而变化。实验上，人类受试者的过度换气导致血流量显着减少。在过度通气研究中发现 DV 相对于基线有所降低，但 DV 比率保持不变。还在两个狒狒实验中测试了升高和降低流量的效果，其中 Pco(2) 是不同的。观察到 DV 比率存在一定的变异性，但与血流量的变化无关。这提出了与血流（或Pco(2)）变化间接相关的其他因素可能导致DV变化的可能性，在评估实验结果时需要考虑这些影响。
To assess the stability of different measures of receptor occupancy from [C-11]raclopride (a D2 antagonist) studies with positron emission tomography, we analyze data from five test/retest studies in normal volunteers in terms of individual model parameters from a three-compartment model, the distribution volume (DV) and the ratio of DVs from a receptor-containing region of interest to a non-receptor-containing region. Large variations were found in the individual model parameters, limiting their usefulness as an indicator of change in receptor systems. The DV ratio showed the smallest variation. Individual differences were reflected in the greater intersubject variation in DV than intrasubject variation. The potential effects of blood flow on these measurements were addressed both experimentally and by simulation studies using three models that explicitly incorporate blood flow into a compartmental model that also includes receptor-ligand binding. None of the models showed any variation in the DV with changes in blood flow as long as flow was held constant during the simulation. Experimentally, blood flow was significantly reduced by hyperventilation in a human subject. The DV was found to be reduced relative to baseline in the hyperventilation study, but the DV ratio remained unchanged. The effect of elevated and reduced flow was also tested in two baboon experiments in which Pco(2) was varied. Some variability in the DV ratio was observed but was not correlated with changes in blood flow. This raises the possibility that other factors indirectly related to changes in blood flow (or Pco(2)) may cause changes in DV, and these effects need to be considered when evaluating experimental results.