Gatley S J, Desombre E R, Mease R C, Seevers R E, Hughes A, Li J, Pan M L
Department of Radiology, University of Chicago, IL 60637.
Int J Rad Appl Instrum B. 1991;18(7):769-75. doi: 10.1016/0883-2897(91)90016-e.
A triphenylethylene compound [1,1-bis(4-hydroxyphenyl)-2-iodo-2-phenylethylene; IBHPE] has been labeled by halodestannylation with 123I at a specific radioactivity of 13,200 Ci/mmol (by in vitro receptor assay) after HPLC purification. The corresponding 80mBr-labeled compound (BrBHPE), which has a 3-fold higher affinity for the estrogen receptor, was previously prepared and examined as a potential therapeutic radiopharmaceutical exploiting Auger electron toxicity. Stability of IBHPE was a concern because free iodide was generated when HPLC solvents were removed with a stream of nitrogen in a glass vial; however, decomposition was minimal when polypropylene vials were used, and ethanol solutions of [123I]IBHPE were stable for several days at 0-4 degrees C. Tissue distribution studies of IBHPE after intraperitoneal injection to mature female rats showed highest estradiol-inhibitable uptake in the peritoneal estrogen-receptor rich tissues (uterus, ovaries and vagina) at 30 min. Specific uptake (percent dose per gram) in the pituitary, and peritoneal target tissue-to-blood ratios were greater at 2 h than 30 min. In immature female rats, uterus-to-blood ratios of greater than 50, progressively lowered by increasing diethylstilbestrol levels, were obtained. These data demonstrate good binding of IBHPE to the estrogen receptor in vivo, in spite of extensive non specific binding in in vitro estrogen receptor assays. Most of the label in the uterus at 1 h after injection was still unchanged IBHPE. Our results suggest that IBHPE or related 123I-labeled iodovinyl triphenylethylenes could have diagnostic or therapeutic radiopharmaceutical utility.
一种三苯乙烯化合物[1,1-双(4-羟基苯基)-2-碘-2-苯乙烯；IBHPE]经高效液相色谱（HPLC）纯化后，通过用123I进行卤代锡烷化反应进行标记，体外受体测定法测得其比活度为13200居里/毫摩尔。之前制备了对雌激素受体亲和力高3倍的相应80mBr标记化合物（BrBHPE），并将其作为利用俄歇电子毒性的潜在治疗性放射性药物进行了研究。IBHPE的稳定性是一个问题，因为用氮气在玻璃小瓶中吹干HPLC溶剂时会产生游离碘；然而，使用聚丙烯小瓶时分解极少，且[123I]IBHPE的乙醇溶液在0-4℃下可稳定保存数天。对成熟雌性大鼠腹腔注射IBHPE后的组织分布研究表明，在30分钟时，富含雌激素受体的腹膜组织（子宫、卵巢和阴道）中雌二醇抑制性摄取最高。垂体中的特异性摄取（每克组织的百分剂量）以及腹膜靶组织与血液的比值在2小时时比30分钟时更高。在未成熟雌性大鼠中，子宫与血液的比值大于50，随着己烯雌酚水平的升高而逐渐降低。这些数据表明，尽管在体外雌激素受体测定中有广泛的非特异性结合，但IBHPE在体内与雌激素受体具有良好的结合。注射后1小时子宫内的大部分标记物仍为未变化的IBHPE。我们的结果表明，IBHPE或相关的123I标记的碘乙烯基三苯乙烯可能具有诊断或治疗性放射性药物的用途。
