^99mTc标记的抗CEA小分子嵌合抗体的体内分布与肿瘤显像  

Radioimmunoimaging and Biodistribution of ^(99m)Tc-labeled Anti-carcinoembyronic Antigen Chimeric Antibody F(ab')2 in Human Colon Carcinoma Xenografts

作　　者：孙立新[1] 赵泽国[1] 遇珑[1] 刘军[1] 韩璐璐[1] 杨治华[1] 孙力超[1] 冉宇靓[1] 

机构地区：[1]中国医学科学院北京协和医学院肿瘤医院肿瘤研究所,分子肿瘤学国家重点实验室,哺乳动物细胞高效表达国家工程实验室,抗体工程药物与肿瘤标志物中关村开放实验室,北京100021

出　　处：《中国肿瘤》2013年第6期461-465,共5页China Cancer

基　　金：“重大新药创制”科技重大专项(2011ZX09102-001-28);“重大新药创制”科技重大专项(2011ZX09401-030)

摘　　要：[目的]采用99mTc标记抗人CEA小分子嵌合抗体Rch24 F(ab’)2,研究其在荷人结肠癌裸鼠体内的生物学分布及放射免疫显像的特征与应用价值。[方法]采用SnCl2直接还原法标记抗体,快速薄层层析法(ITLC)测定抗体的标记效率、放化纯度和体外稳定性,ELISA检测标记抗体的免疫比活性。荷人结肠癌裸鼠尾静脉注射99mTc-Rch24 F(ab’)2后,研究标记抗体在裸鼠体内的生物学分布,并进行肿瘤显像。[结果]99mTc-Rch24 F(ab’)2的标记率为90%,放化纯度>95%。99mTc-Rch24 F(ab’)2的放射比活为840MBq/mg,免疫比活性为65.7%。标记抗体24h时放射性脱落小于5%。荷瘤裸鼠注射99mTc-Rch24 F(ab’)23h后即可观察到肿瘤影像,5~24h均可获得清晰的肿瘤影像,标记抗体在体内呈肿瘤靶向性分布,12h时肿瘤的摄取和多数脏器T/NT比值均达到最高水平。[结论]99mTc-Rch24 F(ab’)2在体内靶向分布于结肠癌肿瘤组织,具有较高的T/NT比值并可在肿瘤局部滞留,注射99mTc-Rch24 F(ab’)25h后肿瘤成像满意。99mTc-Rch24 F(ab’)2在临床肿瘤的放射免疫分子显像诊断中具有良好的应用前景。[Purpose ] To investigate the biodistribution and radioimmunoimaging of 99mTc-Rch24 F（ab＇）2 in human colon carcinoma xenografts in order to provide the basis for radioimmunoimaging and clin- ical application. [Methods] Rch24 F （ab＇）2 was labeled with 99mTc by a stannous chloride reduction method. The radiochemical purity,labeling rate and stability in vitro of 99mTc-labeled Rch24 F（ab＇）2 were determined by ITLC,and immunoreactivity was detected by ELISA. The biodistribution and whole body gamma scintigraphy imaging of 99mTc-labeled Rch24 F（ab＇）2 in human colon carcinoma xenografts were performed. [Results] The labeling rate of 99mTc for Rch24 F（ab＇）2 was 90% ,with radiochemical pu- rity of more than 95%,and the specific reactivity of 99mTc-Rch24 F（ab＇）2 was 840MBq/mg. ｜mmunoreac- tivity of 99mTc-Rch24 F（ab＇）2 was 65.7%. 99mTc-Rch24 F（ab＇）2 showed good stability with less than 5% loss of radioactivity in vitro. It was favorable to get tumor images in 3 hours after injection of 99mTc- Rch24 F （ab＇）2,which could get clear images in 5-24 hours. Application of 99mTc-Rch24 F （ab＇）2 showed the radioactivity targeting distribution of tumor tissues,leading to more ideal radioactivity ra- tio of tumor over non-tumor（T/NT） in 12 hours. [Conclusion] 99mTc-Rch24 F（ab＇）2 particularly be lo- calized in cancer tissue of human colon carcinoma xenografts with the high radioactivity ratio of T/NT. The images of tumor were ohtained successfully after 5 hours after 99mTc-Rch24 F（ab＇）2 injection. 99mTc- Rch24 F（ab＇）2 may be a potential radiopharmaceutical agent for radioimmunoimaging.

关 键 词：CEA 小分子嵌合抗体 放射免疫显像 

分 类 号：R730.3[医药卫生—肿瘤]