125 I标记的抗p185抗体的体外代谢与体内生物学分布

目的：研究^125Ⅰ标记的抗p185抗体（鼠mAb A21、人鼠嵌合抗体A21 scFv-Fc及单链抗体A21 seFv）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SKOV，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SKOV、细胞中的代谢。建立荷SKOV，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：mAb A21，A21 seFv-Fc和A21 scFv对于高表达p185的卵巢癌在体内和体外都具有亲和力，可单用作高表挟D185肿瘤的诊断和治疗。

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

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 SKOV_3 known to highly express surface antigen p185 was assessd by FACS. The metabolism of the antibodies in SKOV_3 was assayed by cellular RIA. The biodistribution of radiolabeled antibodies was evaluated in nude mice bearing SKOV_3 tumor. RESULTS: Cellular RIA demonstrated these antibodies were internalized after binding to cells, followed by degradation and deiodination 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 (SKOV_3) overexpressing p185 in vitro and in vivo and may be used in the diagnosis and treatment of tumors overexpressing p185.