TRACER KINETICS EVALUATING POSITRON TOMOGRAPHY

本提案的目的是审查代谢 心肌基质利用率的表征 用正电子发射法测定时间-活度曲线 断层扫描（PET），但使用14 C标记的试剂。 最近的担忧是， 关于PET标记物描述变化的有效性， 在脂肪酸代谢中作为改变灌注状态的函数。 我们已经证明了14 CO2产生的早期瞬变， 细胞内脂质和脂肪酸库。 与此同时 当发生非稳态加载动力学时，内部，11 C 必须绘制棕榈酸盐时间-活性曲线。 误差 解释可以保证。 此外，在一个完整的、工作的、 体外灌注猪心模型，我们显示了 在回流过程中的底物代谢与 彼前 本建议的目的是探讨 这些差异，并集中在可能的差异， 脉冲标记（与PET一起使用）与平衡标记（与PET一起使用） 我们）。 三种底物将用于对照， 缺血和再流状态。 假设 将测试关于动力学有效性的短寿命 通过使用（U-14 C）重复传统PET实验， 棕榈酸酯、（16- 14 C）葡萄糖、14 C-2-脱氧-D-葡萄糖（DG）和（1- 14 C）乙酸盐。 协议的结构将解决是否在 如脂肪酸和柠檬酸的循环代谢时间- 由脉冲标记产生的活性曲线（假设衰变来自 单个池）准确地预测底物氧化的水平 通过平衡标记测量。 在相关研究中，数学 将采用建模来确定14 C时间活性是否 曲线可由单个或多个池动力学描述， 这些碳库的大小是否会因为 在有氧、缺血或再灌注状态的局部灌注中。 在碳水化合物代谢的情况下，我们将讨论是否DG 在心肌中的捕获准确地反映了恩布登。 Meyerhof 代谢至其葡萄糖氧化和/或乳酸的终点 生产是否14 C-葡萄糖通过脉冲标记是最好的描述 以及这些碳库是否可以出售 与不同流动状态下的生化事件相关。 我们 本提案的最终目的是审查 解释PET衍生的代谢信息， 希望能提供新的临床信心， 将免疫组化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.