DeGrado T R, Holden J E, Ng C K, Raffel D M, Gatley S J
Department of Medical Physics, University of Wisconsin, Madison 53706.
Eur J Nucl Med. 1988;14(12):600-6. doi: 10.1007/BF00251783.
Time courses of radioactivity (residue curves) were obtained following bolus injection into working rat hearts of two 125I-labeled long chain fatty acids: 16-iodohexadecanoic acid (IHDA) and 15-p-iodophenylpentadecanoic acid (IPPA). Residue curves were analyzed in terms of a rapid vascular washout component, an early tissue clearance component, and a very slow late component. For IHDA and IPPA in control hearts, early myocardial clearance kinetics were rate limited by the diffusion of catabolites. Sensitivity of the kinetics to impaired fatty acid oxidation was examination by pretreatment of animals with 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). Decreased fatty acid oxidation was indicated in IHDA and IPPA residue curves by a decrease in the relative size of the early clearance component. Analysis of radiolabeled species in coronary effluent and heart homogenates showed that back diffusion of IPPA was slower than that of IHDA; this discrepancy was most apparent in POCA hearts. In vitro binding assays suggested higher tissue:albumin relative affinity for IPPA than for IHDA. Thus, IPPA early clearance kinetics were more closely related to the clearance of labeled catabolite(s) and were therefore more sensitive to the oxidation rate of long chain fatty acids.
将两种125I标记的长链脂肪酸：16-碘十六烷酸（IHDA）和15-对碘苯基十五烷酸（IPPA）一次性注射到正常工作的大鼠心脏后，获得了放射性的时间进程（残留曲线）。根据快速血管清除成分、早期组织清除成分和非常缓慢的晚期成分对残留曲线进行了分析。对于对照心脏中的IHDA和IPPA，早期心肌清除动力学受代谢产物扩散的速率限制。通过用2[5(4-氯苯基)戊基]环氧乙烷-2-羧酸盐（POCA）预处理动物来检测动力学对脂肪酸氧化受损的敏感性。在IHDA和IPPA残留曲线中，早期清除成分的相对大小减小表明脂肪酸氧化减少。对冠状动脉流出物和心脏匀浆中放射性标记物质的分析表明，IPPA的反向扩散比IHDA慢；这种差异在POCA处理的心脏中最为明显。体外结合试验表明，组织与白蛋白对IPPA的相对亲和力高于对IHDA的相对亲和力。因此，IPPA的早期清除动力学与标记代谢产物的清除更密切相关，因此对长链脂肪酸的氧化速率更敏感。
