Objective The aims of the study were to find out the optimal131I labeling method with 17-allylamino.17-demethoxygeldanamycin(17-AAG)and also to study its biodistribution in animals.Methods 131I-17-AAG was prepared by the reaction of 17-AAG with Na131I in the presence of hydrogen peroxide.The labeling efficiency and the stability of 131I-17-AAG were measured by paper chromatograph.The biodistribution in the ICR normal mice was observed by the blood samplings and major organs that were taken out from mice at 0.5,1,4,8,24 h after131I-17-AAG injection through tail veins.Vχ2 tumor was also implanted in rabbit liver for in vivo imaging with SPECT.Results The optimal labeling conditions of 17-AAG with131I were determined.The labcling efficiency was 85.65%.The radiochemical purity of 131I-17-AAG in acetoacetate solution was(96.51±0.80)%after purification and its radiochemical purlty in normal saline solution was(95.57±0.09)%.The radiochemieal purity could keep to 90%in normal saline after 5 d at 4℃.The biodistribution study in normal mice showed that the uptake ( percentage activity of injection dose per gram of tissue,%ID/g)in liver and kidney was less than that in cholecyst[(3.0963±1.3394)%ID/g ] at 0.5 h post-injection.and the uptake in stomach and intestine reached to the highest level at 4 h post-injection.The SPECT images showed that the 131I-17-AAG was obviously concentrated in the tumor after injection at 2 h and 4 d,6 d,14 d with the highest tumor to non-tumor(T/NT)radioactivity ratio of 10.36.Conclusions The labeling method of 17-AAG with131I was suceessfully established.The 131I-17-AAG in normal saline had a good stability.The main biodistribution in mice was in digestive system and was excreted through the intestinal tract.The SPECT images showed that 131I-17.AAG might be a potential target-directed agent to the tumor.%目的 建立131I标记17-丙烯胺基-17.去甲氧基格尔德霉素(17-AAG)的方法,并观察其在动物体内的生物分布.方法 采用过氧化氢法对17-AAG进行131I标记.测定131I.17.AAG注射后0.5,1,4,8和24 h在ICR健康小鼠体内的生物分布,通过显像动态观察131I-17-AAG在兔Vχ2肝癌模型中的分布.结果 建立了131I过氧化氢法标记17-AAG的最佳条件,131I-17-AAG标记率达85.65%,纯化后其乙酸乙酯相、生理盐水水溶液和4℃下放置5 d的生理盐水水溶液的放化纯分别为(96.51±0.80)%,(95.57±0.09)%和(90.96±1.29)%.尾静脉注射131I-17-AAG,健康ICR小鼠胆囊的摄取(每克组织百分注射剂量率,%ID/g)在0.5 h达到峰值(3.0963±1.3394)%ID/g,胃和小肠的摄取均在4 h达到高峰,24 h时肠道放射性明显减少,肝、肾摄取较少.瘤体给药后于2 h和4,6,14 d进行显像,可见131I-17-AAG在兔肿瘤中持续浓聚,肿瘤/非肿瘤组织放射性(T/NT)比值分别为10.36,3.62,4.32和3.50,其他脏器未见显影.结论 成功建立了131I-17-AAG标记方法,标记物保留了17-AAG生物学活性,体外稳定性好.兔肝肿瘤间质给药提示131I-17-AAG对肿瘤具有理想靶向性作用.
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