Hanson R N, Ghoshal M, Murphy F G, Rosenthal C, Gibson R E, Ferriera N, Sood V, Ruch J
Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, MA 02115.
Nucl Med Biol. 1993 Apr;20(3):351-8. doi: 10.1016/0969-8051(93)90058-3.
In this study we prepared and evaluated a derivative of estradiol with an ethyl group at the 11 beta-position and an E-iodovinyl group at the 17 alpha-position. This new ligand binds to the estrogen receptor with an affinity slightly less than estradiol (RBA = 43%) at 0 degree C but much greater (RBA = 890%) at 25 degrees C. The 125I-labeled derivative was obtained by radioiododestannylation of the tri-n-butylstannyl precursor in good radiochemical yield with a specific activity exceeding 1500 Ci/mmol. The tissue distribution in immature female rats was evaluated over a 48 h period to determine uterine uptake and selectivity. Peak uterine uptake at 2 h was 6% ID/g and was significantly greater than that of [3H]estradiol, 2.4% ID/g. Substantial uptake in the uterus was still present at 48 h (2.4% ID/g). Co-administration of estradiol reduced the uptake at 2 and 24 h by 85%. Uterus-to-plasma ratios increased with time, from about 25:1 at 2 h to nearly 90:1 at 48 h. The affinity, ease of radiosynthesis and tissue distribution of the 17 alpha-E-[125I]iodovinyl-11 beta-ethyl-estradiol suggest that further evaluation of this agent as an imaging agent for estrogen-receptor-positive breast cancer is warranted.
在本研究中，我们制备并评估了一种雌二醇衍生物，其在11β位带有一个乙基，在17α位带有一个E-碘代乙烯基。这种新配体与雌激素受体结合，在0℃时亲和力略低于雌二醇（相对结合活性RBA = 43%），但在25℃时则高得多（RBA = 890%）。通过三正丁基锡前体的放射性碘脱锡反应，以良好的放射化学产率获得了125I标记的衍生物，其比活超过1500 Ci/mmol。在48小时内评估了未成熟雌性大鼠的组织分布，以确定子宫摄取和选择性。2小时时子宫摄取峰值为6% ID/g，显著高于[3H]雌二醇的2.4% ID/g。48小时时子宫仍有大量摄取（2.4% ID/g）。同时给予雌二醇可使2小时和24小时时的摄取降低85%。子宫与血浆的比值随时间增加，从2小时时的约25:1增加到48小时时的近90:1。17α-E-[125I]碘代乙烯基-11β-乙基雌二醇的亲和力、放射合成的简易性和组织分布表明，有必要进一步评估该试剂作为雌激素受体阳性乳腺癌成像剂的性能。
