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

为了确定放射性标记的单抗在结肠癌辅助治疗中的作用，我们用放射性标记单抗H-15治疗剂量进行了临床前研究。120只小鼠脾内注射100，μCi/1μg的I-131标记单抗H-15(低剂量)或500μCi/1μg(高剂量)。另取脾内注射1周后的60只小鼠作为对照。高剂量I-131标记单抗H-15组肝转移瘤总重量明显低于低剂量组和对照组。高剂量I-131标记单抗H-15组的肝转移瘤/肝和肝转移瘤/血的比值均高于低剂量组。大剂量I-131标记NAB H-15组小鼠的存活率显著高于低剂量组和对照组。另180只小鼠在脾内注射1周后，分别给予500μCi/1μg的I-131标记NAB H-15，5天20 mg/kg的5-FU和亚叶酸钙(LV)(低浓度)，或5天(40 mg/kg)的5-FU和LV(高浓度)。I-131标记NAB H-15组的肝肿瘤细胞总重量明显低于5 FU/LV高浓度组和5 FU/LV低浓度组。高剂量I-131标记NAB H-15组的存活率明显高于5-FU/LV高剂量组和低浓度5-FU/LV组。结论：I-131标记mAb1H-15可替代5-FU/LV用于结肠癌全切除术后的辅助治疗。

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.