放射性碘标记CL-3体外肿瘤细胞结合及瘤内注射动物实验研究

The binding of radioiodinated CL-3 monoclonal antibody with tumor cells in vitro and radioactivity distribution in tumor-bearing mice after intratumor administration

为评价瘤内注射(131)~I 标记单抗对提高肿瘤放射免疫治疗效果的作用,用(125)~I 标记抗人结肠癌单抗 CL-3,测定与人结肠癌细胞系 LS174T 及人胃印戒细胞癌细胞系 KATOⅢ的结合率。用34只 LS174T 荷瘤裸鼠,在瘤内注射(131)~I-CL-3后1、3、5、17天进行体内分布与放射免疫显像,以腹腔注射及(131)~I-正常鼠 IgG 瘤内注射组作对照。结果:(131)~I-CL-3与LS174T 及 KATOⅢ细胞结合率达73%;荷瘤裸鼠的瘤/非瘤比值瘤内注射组比腹腔内注射组大2～7倍;每克组织结合注入量的百分数瘤内注射组比腹腔内注射组大2倍多,比(131)~I-IgG 瘤内注射组大5～7倍,且放射免疫显像图清晰。故瘤内注射是提高放射免疫治疗效果的重要途径。单抗标记物在瘤内的存留主要是免疫结合,而不是 IgG 的非特异结合。

PURPOSE The intratumor injection is studied as a means to enhance the effect of radioimmunotherapy (RAIT). METHODS Anti-colorectal monoclonal antibody (McAb) CL3 was labeled with ^(125)I/^(131)I.In vitro,the binding index of ^(125)I-CL-3 with LS 174T human colon adenocarcinoma cell line and KATOⅢ human gastric carcinoma cell line was evaluated by binding as- say.In vivo,^(131)I-CL-3 was injected intratumor (IT) or intraperitoneally (IP) to 34 nude mice bearing tumor LS 174T xenografts.After 1,3,5,17days of administration,radioimmunodetection (RAID) and tissue distribution were observed.RE- SULTS ^(125)I-CL-3 binding capacity with LS 174T and KATOⅢ were both about 73%.The percentage of the injected dose/gram tissue (% ID/g) of ^(131)I-CL-3 in tumor in the IT group was over 2 fold higher than that of the IP group and 5～7 fold higher than that of normal mouse IgG IT control group.In RAID,IT mice likewise showed clearer images in tumors.CONCLUSIONS It is expected that regional therapy by IT might be a suitable method to overcome the drawback and limitation of systemic RAIT.The retention of ^(131)I-CL-3 in tumor was a result of specific antibody binding rather than nonspecific binding of mouse IgG.