【摘要】 目的:建立131I标记热休克蛋白90抑制剂17-丙烯胺基-17-去甲氧基格尔德霉素(17-AAG)的方法,探讨其标记条件。方法:采用放射性碘标记氯胺-T法标记17-AAG,并研究其在ICR正常小鼠体内的生物分布。结果:131I氯胺-T法标记17-AAG的最佳条件为:17-AAG乙醇溶液40μl(含17-AAG 5μg),0.5 mol.L-1磷酸盐缓冲液50μl(pH7.5),Na131I溶液20μl,氯胺-T30μg.(15μl)-1(用pH7.5的0.05 mo.lL-1PB溶解),25℃反应50 s,偏重亚硫酸钠40μg.(20μl)-1(用pH7.5的0.05 mo.lL-1PB溶解)中止反应。标记率约为53.1%,经乙酸乙酯纯化后所得标记物的放射化学纯度>90%;其生理盐水溶液4℃放置5 d,放射化学纯度大于90%。小鼠尾静脉注射131I-17-AAG后0.5 h131I-17-AAG在胆囊达到高峰(369.44±147.81)%ID.g-1,肝脏中仅有(2.23±0.50)%ID.g-1,说明对肝脏毒性小。结论:热休克蛋白90抑制剂17-AAG的标记方法操作简便,反应时间短。更多还原

【Abstract】 Objective To study the method for labeling 17-allylamino,17-demethoxygeldanamycin(17-AAG) with 131I and its biodistribution in normal mice.Methods 131I17-AAG was prepared by the reaction of 17AAG with Na 131I in the presence of chloramines-T.The conditions of labeling,the stability of 131I-17AAG and the biodistribution in normal mice were investigated.Results To search for the optimal conditions,5μg 17AAG dissolved by 40μl alcohol,50μl 0.5mol·L-1 phosphate buffer saline(pH 7.5),20μl Na 131I(185 MBq·ml-1),chloramines-T(2 g·L-1) dissolved by 0.05mol·L-1 phosphate buffer(pH 7.5) were mixed at 25 ℃ for 50 seconds.After the labeling reaction,an excess of sodium metabisulfite dissolved by 0.05mol·L-1 phosphate buffer(pH 7.5) was added to terminate the reaction.The average labeling efficiency was around 53.1%.The radiochemical purity of 131I-17-AAG was over 90% after purification.131I-17-AAG showed the stability above 90% in saline up to 5d at 4 ℃.The biodistribution study in normal mice showed that there was high uptake in cholecyst,stomach and intestine.Conclusion Our preliminary results demonstrate that the labeling of 131I-17-AAG is simple and successful.Further study is going on.更多还原