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单克隆抗体 (mAb) 在结肠癌辅助治疗中的功效，我们使用治疗剂量的 I-131 标记的 mAb H-15 对先天性无胸腺小鼠的人类结肠癌肝微转移进行了临床前研究。脾内注射一周后，一百二十只小鼠静脉注射 100μCi/1μg。 I-131标记的mAb H-15（低剂量）或500μCi/1μg（高剂量）其他60只小鼠脾内注射一周后的高剂量I-131的肝转移瘤总重量。标记mAb H-15组的肝转移/肝脏和肝转移/血液在统计学上低于低剂量组或对照组。高剂量I-131标记mAb H-15组比例高于低剂量组，高剂量I-131标记nAb H-15组存活率显着高于低剂量组和对照组。脾内注射一周后，对 180 只小鼠进行静脉注射 500 μ Ci/1 μg I-131 标记的 nAb H-15，为期 5 天腹膜内注射。 20mg/kg 5-FU 和甲酰四氢叶酸 (LV)（低浓度），或 5 天腹腔注射 40mg/kg 5-FU 和 LV（高浓度） I-131 的肝脏代谢物总重量。标记nAb H-15组的存活率显着低于5FU/LV高浓度组或5FU/LV低浓度组。我们的结论是，I-131 标记的 mAb 1H-15 疗法可能是结肠癌完全切除后辅助治疗中 5 FU/LV 治疗的替代方案。