放射性碘标记的（E）-18-碘-17-十八碳烯酸作为心肌显像碘代烯基脂肪酸模型的合成与评价

Synthesis and evaluation of radioiodinated (E)-18-iodo-17-octadecenoic acid as a model iodoalkenyl fatty acid for myocardial imaging.

作者信息

Knapp F F, Goodman M M, Kabalka G W, Sastry K A

出版信息

J Med Chem. 1984 Jan;27(1):94-7. doi: 10.1021/jm00367a021.

Abstract

125I-labeled (E)-18-iodo-17-octadecenoic acid (13) has been prepared and evaluated in rats to determine the myocardial uptake and retention and degree of in vivo deiodination of this model iodovinyl-substituted fatty acid, which contains no structural perturbation to inhibit metabolism. This new agent was prepared by NaI-chloramine-T treatment of (17-carbomethoxyheptadec-1-en-1-yl)boronic acid (11) prepared by catecholborane treatment of methyl 17-octadecynoate (10), followed by basic hydrolysis to the free acid (13). The pivotal substrate, 17-octadecynoic acid (9), was prepared by two new routes. The 125I-labeled acid 13 showed high myocardial uptake (1 h, 1.90-2.28% dose/g) with 45% washout after 2 h but lower heart/blood ratios in comparison to analogues containing the tellurium heteroatom. Deiodination was low for the first 2 h after injection (2 h, 61% dose/g). Excellent myocardial images were obtained in a dog with the 123I-labeled agent.

摘要

已制备了125I标记的（E）-18-碘-17-十八碳烯酸（13），并在大鼠体内进行评估，以确定该模型碘代乙烯基取代脂肪酸的心肌摄取、滞留情况以及体内脱碘程度，该脂肪酸不存在抑制代谢的结构扰动。这种新试剂是通过用NaI-氯胺-T处理（17-甲氧羰基十七-1-烯-1-基）硼酸（11）制备而成，（11）是由儿茶酚硼烷处理17-十八碳炔酸甲酯（10）后得到的，然后经碱水解得到游离酸（13）。关键底物17-十八碳炔酸（9）通过两条新路线制备。125I标记的酸13显示出较高的心肌摄取（1小时，1.90 - 2.28%剂量/克），2小时后有45%的洗脱，但与含碲杂原子的类似物相比，心脏/血液比值较低。注射后最初2小时内脱碘率较低（2小时，61%剂量/克）。用123I标记的试剂在一只狗身上获得了出色的心肌图像。