^131Ⅰ标记17-丙烯胺基-17-去甲氧基格尔德霉素的制备及生物分布  

Labeling method of 17-allylamino, 17-demethoxygeldanamycin with ^131Ⅰ and its biodistribution in experimental animals

作　　者：姜新宇[1] 刘璐[1] 杨敏[2] 高文[1] 陈道桢[1] 罗世能[2] 黄鹰[1] 

机构地区：[1]东南大学核医学技术研究所,南京210009 [2]江苏省原子医学研究所

出　　处：《中华核医学杂志》2008年第2期124-127,共4页Chinese Journal of Nuclear Medicine

基　　金：国家自然科学基金（30470500）

摘　　要：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24h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VX2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5d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0．5h达到峰值（3．0963±1．3394）％ID／g，胃和小肠的摄取均在4h达到高峰，24h时肠道放射性明显减少，肝、肾摄取较少。瘤体给药后于2h和4，6，14d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件作用．Objective The aims of the study were to find out the optimal ^131Ⅰ 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 Na^131Ⅰ 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 after ^131Ⅰ-17-AAG injection through tail veins, VX2 tumor was also implanted in rabbit liver for in vivo imaging with SPECT, Results The optimal labeling conditions of 17-AAG with ^131Ⅰ were determined, The labeling efficiency was 85.65%, The radiochemical purity of ^131Ⅰ- 17-AAG in acetoacetate solution was （96. 51 ±0. 80）% after purification and its radiochemical purity in normal saline solution was （95.57 ± 0.09） %, The radiochemical 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 pest-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 with ^131Ⅰ was successfully 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.

关 键 词：抗生素类 抗肿瘤 碘放射性同位素 肝肿瘤 实验性 动物 实验 

分 类 号：R686[医药卫生—骨科学]