Collier T Lee, Hwang Yuying, Ramasamy Ravichandran, Sciacca Robert R, Hickey Kathleen T, Simpson Norman R, Bergmann Steven R
Division of Cardiology, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
J Nucl Med. 2002 Dec;43(12):1707-14.
Fatty acid oxidation defects are being increasingly identified as causes of abnormal heart function and sudden death in children. Children with medium-chain acyl-coenzyme A (acyl-CoA) dehydrogenase defects can metabolize fatty acids labeled in the carboxylic acid end of the compound. Accordingly, our goal was to label a long-chain fatty acid in the omega-position and evaluate its myocardial kinetics.
Heptadecanoic acid, a 17-carbon fatty acid, was labeled in the C-17 position with (11)C by the general process of coupling (11)C-methyliodide to t-butyl-15-hexadecanoate. Yield was approximately 5%-10% end-of-bombardment. Subsequently, evaluation studies were performed on isolated perfused rat hearts and in intact, anesthetized dogs. The myocardial uptake and efflux of 17-(11)C-heptadecanoic acid were compared with those of 1-(11)C-palmitate.
With the exception of delayed efflux of tracer reflecting the temporal delay for beta-oxidation, the washout of 17-(11)C-heptadecanoic acid from the heart mirrored that of 1-(11)C-palmitate in isolated rat hearts and in intact dogs with PET.
17-(11)C-Heptadecanoic acid may be a useful tracer for the identification of defects in fatty acid metabolism in subjects with medium- and short-chain fatty acid oxidation defects.
脂肪酸氧化缺陷日益被认为是儿童心脏功能异常和猝死的原因。患有中链酰基辅酶A(酰基辅酶A)脱氢酶缺陷的儿童能够代谢在化合物羧酸末端标记的脂肪酸。因此,我们的目标是在ω位标记一种长链脂肪酸并评估其心肌动力学。
通过将(11)C-甲基碘与叔丁基-15-十六烷酸酯偶联的一般过程,在17碳脂肪酸十七烷酸的C-17位用(11)C进行标记。轰击结束时的产率约为5%-10%。随后,在离体灌注大鼠心脏和完整的麻醉犬身上进行评估研究。将17-(11)C-十七烷酸的心肌摄取和流出与1-(11)C-棕榈酸的进行比较。
在离体大鼠心脏和用正电子发射断层扫描(PET)检测的完整犬中,除了示踪剂流出延迟反映β氧化的时间延迟外,17-(11)C-十七烷酸从心脏的清除与1-(11)C-棕榈酸的相似。
17-(11)C-十七烷酸可能是一种有用的示踪剂,用于识别患有中链和短链脂肪酸氧化缺陷的受试者的脂肪酸代谢缺陷。