^(125)I标记的抗p185抗体的体外代谢与体内生物学分布  

Metabolism of ^(125)I labeled anti-p185 antibodies in vitro and their biodistribution in vivo

作　　者：汪海洋[1] 刘海波[1] 董艳秋[1] 杨建虹[1] 程联胜[1] 刘兢[1] 

机构地区：[1]中国科学技术大学生命科学学院细胞与分子免疫学实验室,安徽合肥230027

出　　处：《细胞与分子免疫学杂志》2005年第5期591-594,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家高技术研究发展计划(863)资助项目(No.2004AA215260)

摘　　要：目的:研究125I标记的抗p185抗体(鼠mAbA21、人鼠嵌合抗体A21scFv-Fc及单链抗体A21scFv)在体外的细胞代谢和在体内的生物学分布,为其在诊断和治疗高表达p185肿瘤的临床应用提供依据。方法:通过FACS检测抗体是否与高表达膜表面抗原p185的SKOV3特异结合。采用氯胺T法进行碘标记抗体,用细胞放射免疫分析实验,检测抗体在SKOV3细胞中的代谢。建立荷SKOV3裸鼠模型,以观察抗体的体内生物学分布。结果:体外细胞代谢实验表明,抗体在与细胞膜表面结合后,进而被内吞入细胞,在细胞内降解和脱碘,最后被分泌出细胞外。体内药物代谢实验表明,抗体在动物体内肿瘤部位出现选择性放射性浓聚,而无关抗体未出现放射性浓聚,呈全身分布。结论:mAbA21,A21scFv-Fc和A21scFv对于高表达p185的卵巢癌在体内和体外都具有亲和力,可望用作高表达p185肿瘤的诊断和治疗。AIM： To study the cellular metabolism （RIA） in vitro and the biodistribution in vivo of ^125Ⅰ labeled anti-p185 antibodies（ murine mAb A21, mouse-human chimeric antibody A21scFv-Fc and single chain antibody A21scFv）, to provide the basis for clinical application in the diagnosis and treatment of tumor overexpressing p185. METHODS： The specificity of binding of these antibodies to SKOV3 known to highly express surface antigen p185 was assessd by FACS. The metabolism of the antibodies in SKOV3 was assayed by cellular RIA. The blodistribution of radiolabeled antibodies was evaluated in nude mice bearing SKOV3 tumor. RESULTS： Cellular RIA demonstrated these antibodies were internalized after binding to cells, followed by degradation and delodinatJon in cells, ^125Ⅰ was then exocytosed, in vivo test showed that these antibodies were concentrated in tumor, but no concentration of control antibody in tumor was found. CONCLUSION： mAb A21, A21 scFv- Fc and A21 scFv can target human ovarian carcinoma cells （ SKOV3 ） overexpressing p185 in vitro and in vivo and may be used in the diagnosis and treatment of tumors overexpressing p185.

关 键 词：代谢 生物学分布 P185 

分 类 号：R817.8[医药卫生—影像医学与核医学]