FLUORODEOXYGLUCOSE KINETICS IN MYOCARDIUM

该提案的总体目标是使用一个孤立的等体积 逆行血液灌注兔心，以评价稳定性， 18F-2-氟脱氧葡萄糖（FDG）示踪动力学中的集总常数 模型和模型准确测量外生 底物供应改变条件下的葡萄糖代谢，冠状动脉 血流和机械工作负荷。 FDG示踪动力学模型 需要三种不同的参数测量来估计葡萄糖 消耗：1）集总常数，2）速率常数描述 模型的三个隔室之间的交换，和3）组织18FDG 内容 在本提案中，我们将测量这三个参数 在体外制剂中，以评价其准确性， 再现性 一旦这些参数已知，集总常数， 与独立测定的血糖和FDG一起 浓度和模型预测的组织FDG-6-PO 4将与 计算外源性葡萄糖消耗量FDG操作方程 来自组织18F含量的单次测量。 另外两种方法 从多个测量值计算心肌葡萄糖消耗 还将评价组织18F含量。 这三个结果 方法将与Fick确定的葡萄糖代谢率进行比较。 在第一个项目中，将研究2- 3 H- 葡萄糖可用于测定葡萄糖膜的速率常数 运输和磷酸化使用FDG模型。 据推测 2- 3 H-葡萄糖只经历膜转运和磷酸化， 由于3 H标记的快速交换， 在2位与未标记的细胞质水， 异构酶反应 在第二和第四个项目中， 集总常数将在以下条件下进行评估： 有证据表明它可能不稳定。 在第二个项目中， 将在存在和不存在胰岛素的情况下评价集总常数 为了改变FDG提取的速率限制步骤， 磷酸化反应至膜转运。 在第四个项目中， 将在改变的情况下评估集总常数的稳定性。 心脏负荷和血流状况。 第三和第五个项目 将评估模型准确测量心肌的能力 葡萄糖消耗在相同的条件下用于 计算集总常数。 这些项目的完成应 提供新的信息，可能有助于使用FDG和正电子 发射断层扫描以量化患者的葡萄糖利用。

The overall goal of this proposal is to use an isolated, isovolumic retrograde blood perfused rabbit heart to evaluate the stability of the lumped constant in the 18F-2-fluoro-deoxyglucose (FDG) tracer kinetic model and the ability of the model to accurately measure exogenous glucose metabolism under conditions of altered substrate supply, coronary blood flow and mechanical workload. The FDG tracer kinetic model requires three different parameter measurements to estimate glucose consumption: 1) the lumped constant, 2) the rate constants describing exchange between the three compartments of the model, and 3) tissue 18FDG content. In the present proposal, we will measure these three parameters in an in vitro preparation to evaluate their accuracy and reproducibility. Once these parameters are known, the lumped constant, together with independently determined plasma glucose and FDG concentrations and the model predicted tissue FDG-6-PO4 will be used with the FDG operational equation to compute exogenous glucose consumption from a single measurement of tissue 18F content. Two other methods of computing myocardial glucose consumption from multiple measurements of tissue 18F content will also be evaluated. The results of all three approaches will be compared to Fick determined glucose metabolic rate. In the first project, the possibility will be investigated that 2-3H- glucose can be used to assess the rate constants of glucose membrane transport and phosphorylation using the FDG model. It is hypothesized that 2-3H-glucose undergoes only membrane transport and phosphorylation in its labeled form because of the documented rapid exchange of 3H-label in the 2 position with unlabeled cytoplasmic water during the hexose isomerase reaction. In the second and fourth projects, the stability of the lumped constant will be evaluated under conditions in which available evidence suggests its possible instability. In the second project, the lumped constant will be evaluated in the presence and absence of insulin in order to change the rate limiting step in FDG extraction from the phosphorylation reaction to membrane transport. In the fourth project, the stability of the lumped constant will be evaluated under altered cardiac loading and blood flow conditions. The third and fifth projects will evaluate the ability of the model to accurately measure myocardial glucose consumption under conditions that are identical to that used for evaluation of the lumped constant. Completion of these projects should provide new information which might help in the use of FDG and positron emission tomography to quantify glucose utilization in patients.