DeGrado T R, Holden J E, Ng C K, Raffel D M, Gatley S J
Department of Medical Physics, University of Wisconsin, Madison.
J Nucl Med. 1989 Jul;30(7):1211-8.
Myocardial extraction and the characteristic tissue clearance of radioactivity following bolus injections of a radioiodinated (125I) long chain fatty acid (LCFA) analog 15-p-iodophenylpentadecanoic acid (IPPA) were examined in the isolated perfused working rat heart. Radioactivity remaining in the heart was monitored with external scintillation probes. A compartmental model which included nonesterified tracer, catabolite, and complex lipid compartments successfully fitted tissue time-radioactivity residue curves, and gave a value for the rate of IPPA oxidation 1.8 times that obtained from steady-state release of tritiated water from labeled palmitic acid. The technique was sensitive to the impairment of LCFA oxidation in hearts of animals treated with the carnitine palmitoyltransferase I inhibitor, 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA). IPPA or similar modified fatty acids may be better than 11C-labeled physiological fatty acids such as palmitate in this type of study, because efflux of unoxidized tracer and catabolite(s) from the heart are kinetically more distinct, and their contributions to the early data can be reliably separated. This technique may be suitable for extension to in vivo measurements with position tomography and appropriate modified fatty acids.
在离体灌注的正常工作大鼠心脏中,研究了静脉注射放射性碘化(125I)长链脂肪酸(LCFA)类似物15-对碘苯基十五烷酸(IPPA)后的心肌摄取及放射性特征性组织清除情况。用外部闪烁探头监测心脏中残留的放射性。一个包含非酯化示踪剂、分解代谢物和复合脂质区室的房室模型成功拟合了组织时间-放射性残留曲线,并得出IPPA氧化速率值,该值是从标记棕榈酸的氚化水稳态释放获得的值的1.8倍。该技术对用肉碱棕榈酰转移酶I抑制剂2-[5-(4-氯苯基)戊基]环氧乙烷-2-羧酸盐(POCA)处理的动物心脏中LCFA氧化损伤敏感。在这类研究中,IPPA或类似的修饰脂肪酸可能比11C标记的生理脂肪酸如棕榈酸盐更好,因为未氧化示踪剂和分解代谢物从心脏的流出在动力学上更明显,并且它们对早期数据的贡献可以可靠地分离。该技术可能适合扩展到用正电子断层扫描和适当的修饰脂肪酸进行体内测量。