TRACER KINETICS EVALUATING POSITRON TOMOGRAPHY

这项提案的目标是审查新陈代谢 心肌底物利用的特征 用正电子发射法绘制时间-活度曲线 断层扫描(PET)，但使用14C标记剂。最近的担忧是 对PET标记描述变化的有效性提出了质疑 作为血流状态改变的函数的脂肪酸新陈代谢。 我们已经证明了14CO2产生的早期瞬变 细胞内的脂类和脂肪酸池。在这段时间里 发生非稳态加载动力学时的内部，11C 必须绘制棕榈酸酯的时间-活度曲线。的错误 解释可能会确保。此外，在一个完好无损的，工作的， 体外灌流猪心模型，我们显示了 回流期间的底物代谢与预测的相反 宠物。这项建议的目的是探讨 并将重点放在可能的差异上 脉冲标记(用于PET)与平衡标记(用于 由我们提供)。三种底物将被用于控制， 猪心模型中的缺血和复流状态。假设 将测试短命运动的有效性 用(U-14C)复制传统的PET实验中的同位素 棕榈酸酯、(16-14C)葡萄糖、14C-2-脱氧-D-葡萄糖(DG)和(1- 14C)醋酸盐。协议将被结构化以解决是否在 脂肪酸和柠檬酸循环代谢时间的情况- 由脉冲标记生成的活动曲线(假设衰变来自 单一熔池)准确预测底物氧化程度 通过平衡标记法进行测量。在相关研究中，数学 将使用建模来确定14C时间活动 曲线可以用单池或多池动力学来描述， 这些碳库的大小是否会因班次的变化而显著改变 在有氧、缺血或再灌流状态的区域灌流中。 在碳水化合物代谢的情况下，我们将解决DG 被困在心肌中准确地反映了Embden。迈耶霍夫 代谢到葡萄糖氧化和/或乳酸的终点 脉冲标记法生产~(14)C-葡萄糖是最好的描述 按单个碳池与多个碳池比较，以及这些碳池是否可以出售 与不同流动状态下的生化事件相关。我们的 本提案的最终目的是审查 解释PET获得的代谢信息，并在这样做的过程中 希望在翻译这些内容时能提供新的临床信心 将放射性数据转化为有意义的亚细胞事件。

The objective of this proposal are to review the metabolic characterization of myocardial substrate utilization derived from time-activity curves using the methods of positron emission tomography (PET) but with 14C labeled agents. Recent concern has been raised about the validity of PET markers to describe changes in fatty acid metabolism as a function of altered perfusion states. We have demonstrated early transients of 14CO2 production within intracellular lipid and fatty acids pools. Over this same time internal when nonsteady state loading kinetics are occurring, 11C palmitate time-activity curves must be developed. Errors of interpretation might ensure. Moreover, in an intact, working, extracorporeally perfused pig heart model, we showed trends in substrate metabolism during reflow opposite to those predicted by PET. The aims of this proposal are to explore the reasons for these discrepancies and to focus on possible differences between pulse labeling (as used with PET) vs equilibrium labeling (as used by us). Three species of substrates will be employed at control, ischemia, and reflow states in the pig heart model. Hypotheses will be tested regarding the kinetic validity of short lived isotopes by reduplicating traditional PET experiments using (U-14C) palmitate, (16-14C) glucose, 14C-2-deoxy-D-glucose (DG), and (1- 14C) acetate. Protocols will be structured to address whether in the case of fatty acid and citric acid cycle metabolism time- activity curves generated by pulse labeling (assuming decay is from a single pool) accurately predict the level of substrate oxidation measured by equilibrium labeling. In related studies, mathematical modeling will be employed to determine whether 14C time-activity curves can be described by single or multiple pool kinetics and whether these carbon pool sizes are significantly altered by shifts in regional perfusion from aerobic, ischemic or reperfused states. In the case of carbohydrate metabolism we will address whether DG trapping in heart muscle accurately reflects Embden. Meyerhof metabolism to its end-points of glucose oxidation and/or lactate production whether 14C-glucose by pulse labeling is best described by single vs multiple carbon pools and whether these can be sell correlated with biochemical events at different flow states. Our ultimate purpose in this proposal is to review any limitations in interpreting PET-derived metabolic information and in so doing hopefully provide new clinical confidence in translating these scintigraphic data into meaningful subcellular events.