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抗乳腺癌单克隆抗体mAb109的放射性标记与生物评价

Radiolabelling and Biological Evaluation of 99Tcm-mAb109 Against Breast Cancer

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【作者】 翟士桢李囡李振甫谢卿张宏杜进杨志

【Author】 ZHAI Shi-zhen,LI Nan,LI Zhen-fu,XIE Qing,ZHANG Hong,DU Jin,YANG Zhi(Key Laboratory of Carcinogenesis and Translational Research of Ministry of Education,Department of Nuclear Medicine, Peking University School of Oncology,Beijing 100142,China)

【机构】 北京大学临床肿瘤学院北京肿瘤医院北京市肿瘤防治研究所核医学科,恶性肿瘤发病机制及转化研究教育部重点实验室中国原子能科学研究院同位素研究所中国同辐股份有限公司

【摘要】 目的探索单克隆抗体mAb109的标记方法,并进行荷瘤动物模型的生物分布和显像研究。方法采用2-巯基乙醇(2-mercaptoethanol,2-ME)法还原单克隆抗体mAb109,并测定还原抗体浓度和巯基含量。通过葡庚糖转络合法用放射性核素99Tcm标记mAb109,测定标记抗体的标记效率和稳定性。建立乳腺癌动物模型,并进行体内分布和显像研究。结果还原抗体保持了较高的完整性,平均每分子抗体含有5.38个巯基。葡庚糖转络合法标记mAb109具有较高的标记率(>90%)和体外稳定性。标记抗体在肿瘤部位有显著的富集,且具有较长的滞留时间。荷瘤动物模型注射99Tcm-mAb109后,可以得到清晰的肿瘤影像。结论99Tcm-mAb109具有较高的标记效率,对所采用的葡萄糖调节蛋白78(glucose-related protein 78,GRP-78)阳性动物模型具有一定的靶向性。

【Abstract】 Objective To investigate the radiolabelling method of 99Tcm-mAb109 against breast cancer,and evaluate its biodistribution and imaging property on tumor-bearing animal model.Methods Monoclonal antibody mAb109 was reduced by 2-mercaptoethanol,the concentration of reduced antibody and the number of sulfhydroxyl group on reduced antibody were determined.The radiolabelling of mAb109 with 99Tcm was carried out by using transchelating method through glucohepatonate.The labeling yield and stability of radiolabelled mAb109 were measured.The biodistribution and imaging study of 99Tcm-mAb109 were carried out on a breast tumor-bearing animal model.Results The reduced antibody mAb109 remained high integrity.The average of 5.38 sulfhydroxyl groups per reduced antibody was detected.The radiolabelling yield of 99Tcm-mAb190 was more than 90%,and 99Tcm-mAb190 was very stable in vitro.Radiolabelled antibody significantly accumulated on tumor sites and remained for long time.Tumor-bearing animal model showed clear imaging after injection of 99Tcm-mAb109.Conclusion The radiolabelling method of 99Tcm-mAb109 is successfully established,and 99Tcm-mAb109 shows potentially targeting characters for animal model borne glucose-related protein 78 positive breast tumors and is worthy for further study.

【基金】 国家自然科学基金(81172083)
  • 【文献出处】 标记免疫分析与临床 ,Labeled Immunoassays and Clinical Medicine , 编辑部邮箱 ,2013年01期
  • 【分类号】R737.9
  • 【被引频次】1
  • 【下载频次】111
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