KINETICS OF MUSCLE METABOLISM BY POSITRON TRACERS

区域血流和代谢的正电子发射断层扫描(PET) 在心脏、大脑和肿瘤组织中引入了一类新的示踪剂 在不破坏的情况下记录完整的、功能正常的器官中的细胞事件 对组织的影响。目前，聚酯的进一步发展 技术因其半定量的性质而受阻。广泛的目标 这个项目的目的是利用正电子的独特特性 发射同位素用于肌肉代谢的定量研究和 体内代谢与功能的相关性。先前的实验 已经证明了葡萄糖类似物的实用性 [18F]-2-脱氧-2-氟-D-葡萄糖(FDG)快速动力学分析 心脏和骨骼肌摄取葡萄糖与器官的关系 功能，但这项技术需要进一步验证。中的放射性 组织与FDG输入功能一起在 一秒一秒地计算。这项技术不仅提供了可靠的数据 动力学建模，但也是检验假设的一种手段，即 用于匹配工作和底物C3利用率的反馈系统 节拍时间刻度。分离的工作大鼠心脏将用于 将示踪剂摄取的动力学与直接测量 控制条件下和特定条件下的葡萄糖利用率 扰动包括竞争底物、葡萄糖的刺激 胰岛素转运和缺血/再灌流。该制剂在体内的应用 骨骼肌技术将利用兔的后肢进行控制 在正常血糖/高胰岛素钳夹期间或期间 收缩活动增强。对于心脏和骨骼肌来说， 类似物和葡萄糖的动力学差异在于 细胞内的磷酸化和去磷酸化将通过 己糖激酶Km和Vmax的直接生化测定 葡萄糖6-磷酸酶为葡萄糖和FDG。这些分析寻求直接 修正系数的关键组成部分发生变化的证据 跟踪到Tracee(集中常量)。酶活性的测定和 细胞内代谢产物水平将被用来评估 动力学分析。预计我们将获得关于以下方面的定量数据 体内的葡萄糖代谢，进而提供关键的信息 胰岛素在肌肉和底物代谢中的作用 组织活力参数对缺血心肌再灌流的影响。

Positron emission tomography (PET) of regional blood flow and metabolism in heart, brain and neoplastic tissue has introduced a new class of tracers to record cellular events in intact, functioning organs without destruction of the tissue. At the present time, further development of the PET technique is hampered by its semi-quantitative nature. The broad objective of this project is to exploit the unique characteristics of positron emitting isotopes for the quantitative study of muscle metabolism and for the correlation between metabolism and function in vivo. Prior experiments have demonstrated the utility of the glucose analog [18F]-2-deoxy-2-fluoro-D-glucose (FDG) for the rapid kinetic analysis of glucose uptake by heart and skeletal muscle as it relates to organ function, but the technique requires further validation. Radioactivity in the tissue is measured together with the FDG input function on a second-by-second basis. This technique not only provides reliable data for kinetic modeling, but also a means to test the hypothesis that there is a feedback system to match work and substrate C3 utilization on a beat-to-beat time scale. The isolated working rat heart will be used to correlate the kinetics of tracer uptake with direct measurements of the rate of glucose utilization under control conditions and after specific perturbations including competing substrates, stimulation of glucose transport by insulin, and ischemia/reperfusion. In vivo application of the technique to skeletal muscle will utilize the rabbit hindlimb under control conditions and during euglycemic/hyperinsulinemic clamps or during periods of increased contractile activity. For both hearts and skeletal muscle, differences in the kinetics of the analog and glucose in terms of intracellular phosphorylation and dephosphorylation will be assessed by direct biochemical measurements of the Km and Vmax of hexokinase and glucose 6-phosphatase for glucose and FDG. These analyses seek direct evidence for changes in key components of the correction factor relating tracer to tracee (lumped constant). Measurements of enzyme activities and intracellular metabolite levels will be used to assess the validity of the kinetic analyses. It is expected that we will obtain quantitative data on glucose metabolism in vivo which, in turn, provide critical information on the action of insulin in muscle as well as substrate metabolism and parameters of tissue viability on reperfusion of ischemic myocardium.