FATTY ACID ANALOGUES FOR MYOCARDIAL IMAGING

一种修饰的放射性标记的脂肪酸，3-甲基-[1- 11 C]-十七烷酸酯（MFA）， 是在我们的实验室开发的局部心肌的评价 新陈代谢. 放射性药物位于心脏 实验动物和人的半停留时间约为100 比棕榈酸盐长一倍。 初步离体器官灌注 实验表明，新陈代谢是通过ω氧化。 的 拟议的研究将描述所采用的两种生化途径， 在这种物质的代谢和动力学行为的 材料以适合于应用于代谢模型的方式。 这 模型将定义必须知道的参数， MFA在心肌中的分布对脂肪代谢的影响 酸在各种情况下。 具体研究将 进行比较MFA棕榈酸酯在离体灌注器官和 狗来表征生化途径，并确定 缺氧、酸中毒和心肌细胞替代底物的可用性 脂肪酸行为 还将在人类志愿者中进行研究， 确定从休息到运动时MFA心肌行为的变化，以及 在进食后。 最后，第二个MFA， 3，15-二甲基-[1- 11 C]-十七烷酸酯将在 离体灌注器官 该物质不应被代谢 无论是β或ω氧化，我提供了一个额外的成像探头， 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.