Van Dort M, Schwendner S W, Skinner R W, Gross M D, Counsell R E
Steroids. 1984 Jul;44(1):85-93. doi: 10.1016/s0039-128x(84)80019-7.
A series of radioiodinated pregnenolone esters was prepared in an effort to find an agent that would be rapidly and selectively taken up by adrenal cortical tissue. Achievement of such a goal would provide the basis for the development of an adrenal imaging agent having several advantages over those agents currently available for clinical use. The radioiodinated esters for this study were readily prepared by treating pregnenolone with the appropriate iodobenzoic acid in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylamino-pyridine (DMAP). The resulting esters were readily labeled with radioiodine by isotope exchange with sodium iodide-125 in pivalic acid. Subsequent tissue distribution studies in rats revealed that those esters displaying the most stability towards hydrolysis achieved the highest concentration in adrenal cortical tissue. For example, the 2,3,5-triiodobenzoate (6) showed an adrenal uptake of 23% of administered dose per gram of tissue at 0.5 hours. The achievement of high levels of radioactivity in the adrenal with this agent at early time periods warrants further evaluation of this agent in other animals.
为了找到一种能被肾上腺皮质组织快速且选择性摄取的药物，制备了一系列放射性碘化孕烯醇酮酯。实现这一目标将为开发一种肾上腺成像剂奠定基础，该成像剂相对于目前临床使用的那些药物具有多个优势。本研究中的放射性碘化酯可通过在二环己基碳二亚胺（DCC）和4-二甲氨基吡啶（DMAP）存在的情况下，用适当的碘苯甲酸处理孕烯醇酮轻松制备。通过与新戊酸中的碘化钠-125进行同位素交换，所得酯很容易用放射性碘标记。随后在大鼠身上进行的组织分布研究表明，那些对水解表现出最高稳定性的酯在肾上腺皮质组织中达到了最高浓度。例如，2,3,5-三碘苯甲酸酯（6）在0.5小时时显示每克组织的肾上腺摄取量为给药剂量的23%。该药物在早期就能在肾上腺中达到高水平的放射性，这值得在其他动物身上对该药物进行进一步评估。
