RADIOIMMUNOTHERAPY FOR HEPATIC MICROMETASTASES FROM HUMAN COLON CANCER IN CONGENITALLY ATHYMIC MICE

先天性无胸腺小鼠结肠癌肝微转移的放射免疫治疗

• 批准号: 12671267
• 负责人: YOSHIDA Kazuhiko
• 金额: $ 1.28万
• 依托单位: THE JIKEI UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671267/
• 关键词: monoclonal antibody; colorectal cancer; liver metastases; micrometastases

To determine the efficacy of radio-labeled monoclonal antibody (mAb) for adjuvant setting in colon cancer, we performed a preclinical study using therapeutic doses of I-131 labeled mAb H-15 in a hepatic micormetastases from human colon cancer in congenitally athymic mice.One hundred twenty mice after one week of intra-splenic injection wore given i. v. injections of either 100, μCi/1μg of I-131 labeled mAb H-15 (low dose) or 500μCi/1μg (high dose). Other 60 mice after one week of intra splenic injection were used as a control arm. The total weight of hepatic metastases of high dose I-131 labeled mAb H-15 group was statistically lower than that of either low dose group or control group. The hepatic metastases/liver and the hepatic metastases/blood ratios of high dose I-131 labeled mAb H-15 group were higher than those of low dose group. The survival rate of high dose I-131 labeled nAb H-15 group was statistically higher than either low dose group or control group.Other one hundred eighty mice after one week of intrasplenic injection were given i. v. injections of either 500 μ Ci/1 μg of I-131 labeled nAb H-15, 5-day intra peritoneal injection of 20mg/kg of 5-FU and leucovorin (LV) (low concentration), or 5-day intra peritoneal injections of 40mg/kg of 5-FU and LV (high concentration). The total weight of hepatic motastases of I-131 labeled nAb H-15 group was significantly lower than that of either high concentration group of 5 FU/LV or low concentration group of 5 FU/LV. The survival rate of high dose I-131 labeled nAb H-15 group was statistically higher than either high concentration group of 5-FU/LV of low concentration group of 5-FU/LV.We conclude that I-131 labeled mAb 1H-15 therapy might be an alternative to 5 FU/LV treatment in the adjuvant therapy after complete resection of colon cancer.

为了确定放射性标记的单克隆抗体（mAb）在结肠癌辅助治疗中的有效性，我们用治疗剂量的I-131标记的mAb H-15对先天性无胸腺小鼠的人结肠癌肝微转移进行了临床前研究。注射100 μCi/1μg I-131标记的mAb H-15（低剂量）或500μCi/1μg（高剂量）。另外60只小鼠脾内注射后1周作为对照组，高剂量I-131标记的mAb H-15组肝转移瘤的总重量显著低于低剂量组和对照组。I131标记的mAb H 15高剂量组的肝转移/肝和肝转移/血比值均高于低剂量组。高剂量I-131标记nAb H-15组小鼠的存活率明显高于低剂量组和对照组。静脉注射500 μ Ci/1 μg I-131标记的nAb H-15，5天腹膜内注射20 mg/kg 5-FU和甲酰四氢叶酸（LV）（低浓度），或5天腹膜内注射40 mg/kg 5-FU和LV（高浓度）。I-131标记的nAb H-15组肝转移酶的总重量显著低于5 FU/LV高浓度组和5 FU/LV低浓度组。高剂量I-131标记的mAb H-15组的生存率显著高于高浓度5-FU/LV组和低浓度5-FU/LV组。因此，I-131标记的mAb H-15治疗结肠癌完全切除术后的辅助治疗可能是5-FU/LV治疗的替代方案。