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人结肠癌异种移植瘤的放射免疫定位;单克隆抗癌胚抗原抗体的广泛纯化方面

Radioimmunolocalization of human colonic cancer xenografts; aspects of extensive purification of monoclonal anti-CEA-antibodies.

作者信息

Sundin A, Enblad P, Ahlström H, Carlsson J, Maripuu E, Hedin A

机构信息

Department of Diagnostic Radiology, Akademiska Sjukhuset, Uppsala University, Sweden.

出版信息

Int J Rad Appl Instrum B. 1991;18(8):891-9. doi: 10.1016/0883-2897(91)90098-6.

Abstract

Tumour-to-normal tissue ratios of i.p. injected 125I-labelled monoclonal antibodies (MAbs), reacting with CEA were determined in nude rats xenografted with human colonic cancer cells (LS 174 T). Two MAbs, I-38S1 and II-16, reactive with the GOLD 1-epitope on CEA were tested. MAb I-38S1 was also tested after additional purification using anion exchange chromatography (thereafter named AEC 38). In the external activity measurements, MAb AEC 38 showed significantly better tumour-to-liver ratios than did MAb II-16 on all 4 days after injection. MAb I-38S1 gave intermediate ratios but was significantly better than II-16 only on day 3. The mean tumour-to-blood ratios were 3.0, 2.6 and 1.5 and the mean tumour-to-liver ratios were 6.6, 4.8 and 3.5 for MAbs AEC 38, I-38S1 and II-16 respectively. Gamma camera registrations in 3 animals on 4 days showed good imaging properties for all three MAbs and the patterns of tissue uptake were consistent with those seen in the external measurements. Furthermore, histopathological and immunohistochemical determinations were performed, showing that MAb II-16 gave about the same spatial binding as the previously analysed MAb I-38S1. The results indicate that additional purification of MAbs using anion exchange chromatography may potentiate tumour uptake in this model.

摘要

在接种了人结肠癌细胞(LS 174 T)的裸鼠中,测定了腹腔注射的与癌胚抗原(CEA)反应的¹²⁵I标记单克隆抗体(MAb)的肿瘤与正常组织的比率。测试了两种与CEA上的GOLD 1表位反应的单克隆抗体I-38S1和II-16。单克隆抗体I-38S1在使用阴离子交换色谱进行进一步纯化后也进行了测试(此后称为AEC 38)。在外部活性测量中,在注射后的所有4天里,单克隆抗体AEC 38的肿瘤与肝脏比率均显著优于单克隆抗体II-16。单克隆抗体I-38S1的比率处于中间水平,但仅在第3天显著优于II-16。单克隆抗体AEC 38、I-38S1和II-16的平均肿瘤与血液比率分别为3.0、2.6和1.5,平均肿瘤与肝脏比率分别为6.6、4.8和3.5。4天内对3只动物进行的γ相机成像显示,所有三种单克隆抗体都具有良好的成像特性,组织摄取模式与外部测量结果一致。此外,还进行了组织病理学和免疫组织化学测定,结果表明单克隆抗体II-16的空间结合与先前分析的单克隆抗体I-38S1大致相同。结果表明,使用阴离子交换色谱对单克隆抗体进行进一步纯化可能会增强该模型中的肿瘤摄取。

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