~(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

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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 of nude mice bearing human colon cancer was studied by using 131I-labeled anti-human colon cancer monoclonal antibody (McAbMC_3) and experimental treatment. The results showed that the specific binding rates of in vitro labeled antibodies were 37.5% and 32.1%, respectively. In the nude mice, 48- to 120-h ECT photographs showed that there were specific concentrations of radioactivity in the tumor sites. The amount of their uptake gradually increased with time, and the tumor development was clear. The appropriate time for imaging was 96-120 hours. When non-specific 131I-NM IgG was administered, the tumor site was seen to be radioactively concentrated and showed a uniform distribution throughout the body. The ratios of tumor tissue to liver and normal intestinal tissue at 120 h were 3.61 and 9.81, respectively, and the tumor localization index was 4.26. Experimental treatment showed that 131I-MC_3 significantly inhibited the growth of tumor compared with the control. The tumor inhibition rate was 90.14% on the 14th day after treatment, which was significantly different from that of the 131I-NM IgG control group. P<0.01). Serum CEA levels in nude mice on the 32nd day after treatment were significantly different from those in the 131I-NM IgG group (P<0.05). Histopathological examination showed that tumors in 131I-MC3 nude mice were massively necrosed after 8 days of treatment. Only a few intact tumor cells were present at the edge of the local tumor. No other normal tissues and organs showed significant radiation damage. This suggests that McAbMC_3 may have good prospects for the diagnosis and targeted treatment of colorectal cancer.
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