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先天性无胸腺小鼠体内人结肠癌肝转移灶中单克隆抗体的放射定位

Radiolocalization of monoclonal antibodies in hepatic metastases from human colon cancer in congenitally athymic mice.

作者信息

Yoshida K, Rivoire M, Divgi C, Welt S, Cohen A M, Sigurdson E R

机构信息

Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.

出版信息

Cancer Res. 1990 Feb 1;50(3 Suppl):862s-865s.

PMID:2297735
Abstract

Intrasplenic injection of the HT-29 LMM metastatic human colon cancer line reproducibly results in hepatic metastasis formation in congenitally athymic mice. HT-29-15, a murine monoclonal antibody (mAb) of the IgG1 class reactive with the HT-29 LMM line, and BL-3, an isotype-matched control antibody, were labeled with 125I. Labeled mAbs were injected i.v. in mice with hepatic metastases, and animals were sacrificed on days 3, 5, and 7. Specific mAb uptake by tumor was significantly greater than nonspecific mAb uptake, as evidenced by specific/nonspecific tumor/blood ratios (radiolocalization indices) of 3.47/1-25.6/1. Relative mAb uptake was greater by the hepatic tumors than by the splenic tumors from day 3 to day 7, although this was significant (P less than 0.05) only on day 7 (5.12 +/- 2.97 versus 1.79 +/- 0.71). Tumor/uninvolved tissue ratios were also significantly greater (P less than 0.05) for the hepatic metastases than for the splenic tumors on day 7 (12.23 +/- 3.85 versus 6.63 +/- 2.63). This murine hepatic metastasis model appears useful for evaluation of localization of mAbs to hepatic metastases from human colon carcinoma.

摘要

将HT - 29 LMM转移性人结肠癌细胞系经脾内注射到先天性无胸腺小鼠体内,可重复性地导致肝转移形成。HT - 29 - 15是一种与HT - 29 LMM细胞系反应的IgG1类鼠单克隆抗体(mAb),BL - 3是一种同型匹配的对照抗体,用125I进行标记。将标记的单克隆抗体经静脉注射到有肝转移的小鼠体内,并在第3、5和7天处死动物。肿瘤对特异性单克隆抗体的摄取明显高于非特异性单克隆抗体的摄取,特异性/非特异性肿瘤/血液比值(放射性定位指数)为3.47/1至25.6/1证明了这一点。从第3天到第7天,肝肿瘤对单克隆抗体的相对摄取高于脾肿瘤,尽管仅在第7天这一差异具有统计学意义(P小于0.05)(5.12±2.97对1.79±0.71)。在第7天,肝转移灶的肿瘤/未受累组织比值也显著高于脾肿瘤(P小于0.05)(12.23±3.85对6.63±2.63)。这种小鼠肝转移模型似乎可用于评估单克隆抗体在人结肠癌肝转移灶中的定位。

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