^(188)Re标记抗CEA单克隆抗体及荷瘤裸鼠治疗实验研究

^(188)Re labelling of the anti-CEA monoclonal antibody and its therapeutic study in nude mice bearing tumor

为建立18 8Re标记抗癌胚抗原 (CEA)单克隆抗体 (McAb )C50 的直接标记方法 ,探讨其标记条件 ,用抗坏血酸还原McAb ,并以葡萄糖酸钠为中间螯合剂 ,以氯化亚锡作还原剂 ,用188Re标记C50 。观察188Re标记McAb的体外稳定性 ,探讨还原剂SnCl2 浓度、螯合剂葡萄糖酸钠浓度、抗体浓度、加入抗体间隔的时间对标记物放化纯度的影响。SPECT显像观察荷瘤裸鼠瘤内注射188Re-C50 后放射性分布 ,对治疗后的瘤体行病理观察。实验结果显示 ,188Re标记C50 的合适条件为 :2 .2— 4 .0g/LSnCl2 、0 .3mol/L葡萄糖酸钠溶液、2 .5× 10 5— 5 .0× 10 5mol/LMcAb ,反应 2h后放化纯度可达 90 %。荷瘤裸鼠瘤内注射188Re -C50 后 ,放射性集中在瘤内 ,2周后瘤体明显缩小 ,镜下观察到肿瘤细胞破裂 ,坏死。

A direct labelling method for anti-CEA monoclonal antibody (McAb), C 50 was labelled with 188Re has been established. Making use of sodium gluconate as chelator, SnCl 2 as reducing agent, the McAb C 50 was reduced by Vitamin C, and then labelled with 188Re. In this process, the in vitro stability of labelled 188Re-C 50 was observed, the concentration of SnCl 2, sodium gluconate, and McAb as well as the affection of interval time of adding McAb on radiochemical purity of labelled C 50 were determined. SPECT imaging was performed to show the biological distribution of 188Re labelled C 50 after injected into the tumor of nude mice. The pathologic study was observed by electron microscopy after therapy. The experimental results showed that the optimal condition for 188Re labelling C 50 was as follows: the concentration of SnCl 2, sodium gluconate and McAb was 2.2-4.0g/L, 0.3mol/L and 2.5×10 5-5.0×10 5mol/L respectively. The labelling efficiency 2h post labelling was as high as 90%. The radioactivity was localized in the tumor after 188Re-C 50 was injected into it, and the tumor began to shrink 2 weeks later, the disruption and necrosis of the tumor cells were observed microscopically.