~(131)I标记抗人结肠癌单克隆抗体MC_3对裸鼠载人肠癌的放射免疫显像和导向治疗研究

用~(131)I标记的抗人结肠癌单克隆抗体(McAbMC_3)对裸鼠载人肠癌进行放射免疫显像诊断和实验性治疗研究。结果显示:体外标记抗体特异性结合率分别为37.5％和32.1％。裸鼠体内在48~120h的ECT照相可见在肿瘤部位均有放射性的特异性浓聚,其摄取量随时间延长逐渐增加,肿瘤显影清晰,显像的合适时间为96～120h。而给予非特异性的~(131)I-NMIgG后肿瘤部位来见放射性浓聚,而呈全身均匀性分布。120h肿瘤组织与肝脏及正常肠组织的比值分别为3.61和9.81,肿瘤定位指数为4.26。实验治疗显示与对照相比~(131)I-MC_3对肿瘤有明显的抑制生长作用,治疗后第14天肿瘤抑制率为90.14％,与~(131)I-NMIgG对照组比较差异极显著(P<0.01)。治疗后第32天裸鼠血清CEA含量与~(131)I-NMIgG组比较差异显著(P<0.05)。病理组织学检查结果显示治疗后8天注射~(131)I-MC_3裸鼠肿瘤呈大片坏死,仅局部肿瘤边缘尚存少数完整的肿瘤细胞,而其它正常组织、器官未见明显辐射损伤。提示McAbMC_3用于肠癌的诊断和导向治疗可能有良好的前景。

RADIOIMMUNOIMAGING AND TARGETING TREATMENT OF ~(131)I-LABELED MONOCLONAL ANTIBODY MC_3 IN NUDE MICE BEARING HUMAN RECTAL CANCER

Radioimmunoimaging and targeting treatment of ~(131)I-labeled specific monoclonal antibody MC_3 against human colon mucoid adenocarcinoma in tumor-bearing nude mice were studied. The specific binding rate of the monoclonal antibody MC_3 to rectal cancer cells in vitro was 37.5% and 32.1%. In nude mice bearing human rectal cancer xenografts a clear image of tumor was obtained by ECT camera between 48-120 hours after injection of laoeled MC_3 and the concentration of MC_3 in tumor increased with time. The optimal imaging time was 96-120 hrs. after injection. Where as injection of ~(131)I-NMIgG in to the nude mice resulted in an equal distribution in the whole body. 120 hours after injection of ~(131)I-MC_3 the tumor/liver and tumor/normal colon distribution raties were 3.61 and 9.81 respectively and the localization index of tumor was 4.26. Targeting treatment of ~(131)I-MC_3 was found to be able to inhibit 90.14% of tumor growth at 14th day after injection as compared with the control groups. The difference was very significant (P<0.01) as compared with the ~(131)I-NMIgG control group. The difference in the amount of CEA in blood serum of nude mice at 32th day after injection of ~(131)I-MC_3 was significant (P<0.05) as compared with the ~(131)I-NMIgG control group. Histopathological examination showed that in the ~(131)I-MC_3 group at 8th day after injection the tumor showed large areas of necrosis, and only a few round cancer cells werw found near the capsule of the tumor. Inradiation damage was observed in other tissues. The results showed that monoclonal antibody MC_3 may be used in localization and targeting treatment of human colon-rectal cancers.