Buckman B O, VanBrocklin H F, Dence C S, Bergmann S R, Welch M J, Katzenellenbogen J A
Department of Chemistry, University of Illinois, Urbana 61801.
J Med Chem. 1994 Jul 22;37(15):2481-5. doi: 10.1021/jm00041a028.
In order to diagnose patients with medium-chain acyl-CoA dehydrogenase deficiency with a noninvasive diagnostic technique such as positron emission tomography, we have developed a synthesis of [omega-11C]palmitic acid. The radiochemical synthesis was achieved by coupling an alkylfuran Grignard reagent (7) with [11C]methyl iodide, followed by rapid oxidative cleavage of the furan ring to the carboxylate using ruthenium tetraoxide. Tissue biodistribution studies in rats comparing [omega-11C]palmitic acid and [1-11C]palmitic acid show that the %ID/g and %ID/organ in the heart tissue after administration of [omega-11C]palmitic acid is approximately 50% greater than after administration of [1-11C]palmitic acid, due to the diminished metabolism of the [omega-11C]palmitic acid. These studies show as well, low uptake in nontarget tissues (blood, lung, kidney, and muscle). PET images of a dog heart obtained after administration of [omega-11C]-and [1-11C]palmitic acid show virtually identical uptake and distribution in the myocardium. The differing cardiac washout of labeled palmitates measured by dynamic PET studies may allow diagnosis of disorders in cardiac fatty acid metabolism.
为了使用正电子发射断层扫描等非侵入性诊断技术诊断中链酰基辅酶A脱氢酶缺乏症患者，我们开发了一种[ω-11C]棕榈酸的合成方法。通过将烷基呋喃格氏试剂（7）与[11C]甲基碘偶联，然后使用四氧化钌将呋喃环快速氧化裂解为羧酸盐，实现了放射化学合成。在大鼠中进行的比较[ω-11C]棕榈酸和[1-11C]棕榈酸的组织生物分布研究表明，由于[ω-11C]棕榈酸的代谢减少，给予[ω-11C]棕榈酸后心脏组织中的%ID/g和%ID/器官比给予[1-11C]棕榈酸后大约高50%。这些研究还表明，非靶组织（血液、肺、肾和肌肉）中的摄取量较低。给予[ω-11C]和[1-11C]棕榈酸后获得的犬心脏PET图像显示心肌中的摄取和分布几乎相同。通过动态PET研究测量的标记棕榈酸盐在心脏中的不同清除情况可能有助于诊断心脏脂肪酸代谢紊乱。
