用抗癌胚抗原单克隆抗体A10的放射性标记嵌合Fab片段对裸鼠胰腺癌异种移植瘤进行放射性定位。

Radiolocalization of pancreatic carcinoma xenografts in nude mice with radiolabeled chimeric Fab fragments of anti-carcinoembryonic antigen monoclonal antibody A10.

作者信息

Kamigaki T, Yamamoto M, Ohyanagi H, Saitoh Y

机构信息

First Department of Surgery, Kobe University School of Medicine, Japan.

出版信息

Pancreas. 1995 Apr;10(3):258-64. doi: 10.1097/00006676-199504000-00007.

DOI:10.1097/00006676-199504000-00007

PMID:7624303

Abstract

Recombinant mouse-human chimeric Fab fragments of anti-carcinoembryonic antigen monoclonal antibody (MAb) A10 react with various GI carcinomas. We tested radiolocalization of pancreatic carcinoma xenografts in nude mice using radiolabeled chimeric A10 Fab fragments, comparing them with murine Fab fragments and parental MAb. For mice injected with chimeric A10 Fab fragments, we obtained significantly higher uptake in tumors than in normal tissues at 24 and 48 h after injection. In addition, tumor/normal tissues labeling ratios for chimeric A10 Fab fragment were significantly greater than those for murine MAb at 24 h postinfusion. However, no significant difference in biodistribution was observed between chimeric and murine Fab fragments. In autoradiography imaging studies, we obtained clearer tumor detection without visible uptake in normal organs for chimeric Fab fragments than for murine MAb. These results suggest that chimeric Fab fragments of A10 could be a potentially useful candidate for radioimmunodetection of pancreatic carcinomas.

摘要

抗癌胚抗原单克隆抗体（MAb）A10的重组小鼠-人嵌合Fab片段可与多种胃肠道癌发生反应。我们使用放射性标记的嵌合A10 Fab片段，在裸鼠中测试了胰腺癌异种移植瘤的放射性定位，并将其与鼠源Fab片段和亲本单克隆抗体进行比较。对于注射了嵌合A10 Fab片段的小鼠，在注射后24小时和48小时，我们在肿瘤中获得的摄取量显著高于正常组织。此外，在输注后24小时，嵌合A10 Fab片段的肿瘤/正常组织标记率显著高于鼠源单克隆抗体。然而，嵌合Fab片段和鼠源Fab片段之间未观察到生物分布的显著差异。在放射自显影成像研究中，与鼠源单克隆抗体相比，我们使用嵌合Fab片段获得了更清晰的肿瘤检测结果，且正常器官中无可见摄取。这些结果表明，A10的嵌合Fab片段可能是胰腺癌放射免疫检测的一个潜在有用候选物。