Weichert J P, Longino M A, Schwendner S W, Counsell R E
J Med Chem. 1986 Sep;29(9):1674-82. doi: 10.1021/jm00159a019.
A series of omega-(3-amino-2,4,6-triiodophenyl)alkanoic acids and the corresponding 1,3-dipalmitoylglycerol 2-[omega-(3-amino-2,4,6-triiodophenyl)alkanoates] were synthesized, radioiodinated with iodine-125, and evaluated for their ability to selectively localize in the liver for potential use as hepatographic imaging agents. Acid analogues 1d and 1e afforded relatively high levels of radioactivity in the liver (45 and 49% injected dose) 5 min after intravenous administration to rats. These acids displayed a marked propensity to become bound to plasma albumin. In contrast, triacylglycerol analogues 10a and 10c did not become immediately associated with plasma albumin but instead rapidly became associated with plasma lipoproteins and showed a different tissue distribution profile than free acids 1a and 1c. Although long-chain triacylglycerol analogues 10d and 10e exhibited some capacity to accumulate in the liver at 5 and 30 min, respectively, analysis of the plasma revealed significant in vivo ester hydrolysis. It would thus appear that liver radioactivity following administration of 10d and 10e was due to uptake of the free acid and not the intact triacylglycerol. Triacylglycerol analogues 10a and 10c, on the other hand, were taken up intact and showed liver accumulations of 25 and 35% of the administered dose at 30 min.
合成了一系列ω-(3-氨基-2,4,6-三碘苯基)链烷酸及其相应的1,3-二棕榈酰甘油2-[ω-(3-氨基-2,4,6-三碘苯基)链烷酸酯]，用碘-125进行放射性碘化，并评估它们在肝脏中选择性定位的能力，以作为潜在的肝脏造影成像剂。酸类似物1d和1e在静脉注射给大鼠后5分钟，在肝脏中产生了相对较高水平的放射性（分别为注射剂量的45%和49%）。这些酸表现出与血浆白蛋白结合的明显倾向。相比之下，三酰甘油类似物10a和10c没有立即与血浆白蛋白结合，而是迅速与血浆脂蛋白结合，并且显示出与游离酸1a和1c不同的组织分布特征。尽管长链三酰甘油类似物10d和10e分别在5分钟和30分钟时表现出一定的在肝脏中蓄积的能力，但血浆分析显示体内存在明显的酯水解。因此，给予10d和10e后肝脏中的放射性似乎是由于游离酸的摄取，而不是完整的三酰甘油。另一方面，三酰甘油类似物10a和10c被完整摄取，在30分钟时肝脏蓄积量分别为给药剂量的25%和35%。
