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作 者:闫平[1] 王荣福[1] 张春丽[1] 郭凤琴[1] 康磊[1] 于明明[1] 崔永刚[1]
机构地区:[1]北京大学第一医院,北京100034
出 处:《肿瘤学杂志》2010年第6期442-445,共4页Journal of Chinese Oncology
基 金:国家自然科学基金(30870729;30900374);教育部教育振兴行动计划特殊专项("九八五"工程:Ⅱ期)资助项目(985-2-056);国家重点基础研究发展计划(973计划)(2006CB705705);高等学校博士学科点专项科研基金(20080001106);北京大学医学物理和工程北京市重点实验室开放基金(2009006)
摘 要:[目的]用131I标记抗人肿瘤分泌IgG轻链单克隆抗体(ATILCMcAb)进行荷瘤裸鼠体内生物分布与显像研究,探讨其在放射免疫显像及靶向治疗中的应用前景。[方法]采用氯胺-T法标记,SephadexG-25柱层析分离纯化,纸层析法测定标记率和放化纯度。BALB/c裸鼠右侧腹股沟皮下注射宫颈癌上皮细胞(HeLa MR),待肿瘤长至1cm左右,进行荷瘤裸鼠体内生物分布与显像实验。对照组为mIgG蛋白。[结果]131I-ATILCMcAb标记率89.9%±4.72%(n=4),放射性比活度1.26MBq/μg,放化纯度98.1%±1.24%(n=4),于4℃冰箱及37℃正常人混合血清存放72h后,放化纯度仍>90%。131I-ATILCMcAb在血中的清除率较131I-mIgG快(P<0.001);除肝、膀胱和股骨外,各组织72h T/NT比值与131I-mIgG比较有显著性差异(P<0.05)。荷瘤裸鼠体内显像实验显示24~72h,ATILCMcAb使肿瘤部位清晰显像。[结论]ATILCMcAb能够通过与肿瘤分泌的IgG特异结合而实现对肿瘤的探测,具有较好的生物学特性,为进一步的放射免疫显像及靶向治疗研究奠定了实验基础。[Purpose] To radioiodinate antihuman tumor-derived IgG light chain monoclonal antibody (ATILCMcAb),to study biodistribution and imaging in nude mice bearing tumor in vivo and to investigate the potentiality of targeted therapy in the future.[Methods] ATILCMcAb was labeled with 131I by the Chloramine-T method and purified through Sephadex G-25 column.BALB/c nude mice were inoculate with HeLa MR cells in the right hind leg.Biodistribution study and SPECT imaging were performed after the tumor growed up to a diameter with 1.0cm meanwhile mIgG as a control.[Results] The labeling efficiencies of 131I-ATILCMcAb reached 89.9%±4.72% (n=4),the specific activity was up to 1.26MBq/μg,and the radiochemical purity was 98.1%±1.24% (n=4).The radiochemical purities of 131I-ATILCMcAb kept highly stability (90%) at 4℃ and 37℃ in human serum within 72hr.131I-ATILCMcAb clearance from blood was faster than 131I-mIgG (P0.001).In comparison with the T/NT ratio of 131I-ATILCMcAb and 131I-mIgG,there was significant difference except liver,bladder and bone (P0.05).SPECT imaging showed that 131I-ATILCMcAb was more clearly imaged from 24h till 72h.[Conclusion] ATILCMcAb is successful in tumor imaging through specially combined to tumor-derived IgG,and has good biological characteristics.It establishes the further experimental foundation for cancer imaging and targeted therapy.
关 键 词:抗人肿瘤分泌IgG轻链单克隆抗体 131I标记 裸鼠 生物分布 显像
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