FATTY ACID ANALOGUES FOR MYOCARDIAL IMAGING

一种修饰的放射性脂肪酸，3-甲基-[1-11C]-十七烷酸(MFA)， 是我们实验室开发的用于评价局部心肌的 新陈代谢。放射性药物定位在中国人的心中 实验动物和人居住一半时间约100 比棕榈酸要长几倍。初步隔离器官灌流 实验表明，代谢是通过omega氧化实现的。这个 拟议中的研究将描述所采用的两种生化途径 在这种物质的新陈代谢和运动行为中 材料以适合应用于代谢模型的方式。这 模型将定义必须已知的参数才能将区域 MFA在心肌中的分布与脂肪的局部代谢 在各种不同的环境下都能产生酸。具体的研究将是 对MFA和棕榈酸酯在隔离灌流器官和 狗的生物化学途径的特征和确定的效果 低氧、酸中毒和心肌替代底物的可用性 脂肪酸行为。研究还将在人类志愿者身上进行，以 建立从休息到运动的MFA心肌行为的变化，以及 吃了一顿饭之后。最后，第二个MFA， 3，15-二甲基-[1-11C]-十六烷酸，将在 隔离的灌流器官。这种物质不应该被代谢成 Beta或omega氧化，我提供了一个额外的成像探头 目的：研究心肌脂肪酸代谢。

A modified radiolabled fatty acid, 3-methyl-[1-11C]-heptadecanoate (MFA), was developed in our laboratory for the evaluation of regional myocardial metabolism. The radiopharmaceutical localized in the hearts of experimental animals and man with a residence half time approximately 100 times longer than palmitate. Preliminary isolated organ perfusion experiments suggested that metabolism was via omega oxidation. The proposed research will characterize both the biochemical pathways employed in the metabolism of this substance and the kinetic behavior of the material in a manner suitable for application to a metabolic model. This model will define the parameters that must be known to relate the regional distribution of MFA in the myocardium to the regional metabolism of fatty acids under a wide variety of circumstances. Specific studies will be performed comparing MFA to palmitate in isolated perfused organs and in dogs to characterize the biochemical pathways and determine the effect of hypoxia, acidosis, and availability of alternative substrates on myocardial fatty acid behavior. Studies will also be performed in human volunteers to establish the changes in MFA myocardial behavior from rest to exercise, and following ingestion of a meal. Finally, a second MFA, 3,15-dimethyl-[1-11C]-hepatadecanoate, will be synthesized and tested in isolated perfused organs. This substance should not be metabolized by either beta or omega oxidation, and my provide an additional imaging probe to study myocardial fatty acid metabolism.