188Re-Hepama-1单克隆抗体荷人肝癌裸鼠模型实验研究

目的 研究188Re-单克隆抗体(简称单抗)Hepama-1在荷人肝癌裸鼠体内生物学分布及肿瘤抑制,为放免治疗提供依据.方法 制备188Re-Hepama-1并测定其标记率及体外稳定性.将40只荷瘤裸鼠用完全随机法分为5组:生理盐水对照组、188ReO4-瘤内注射组、188Re标记健康小鼠IgG(188Re-mIgG)瘤内注射组、188Re-Hepama-1静脉给药组、188Re-Hepama-1瘤内注射组.注射后48 h每组各处死3只,测定肿瘤和肝等重要器官的放射性,用每克组织百分注射剂量率(%ID/g)表示;分别于治疗后1,2,3及4周计算肿瘤体积,与治疗前肿瘤体积进行对比;治疗后4周,每组各处死3只荷瘤裸鼠,观察肿瘤细胞超微结构改变及组织病理学改变.结果 188Re-Hepama-1标记率为85%,放化纯＞95%.注射后48h瘤内注射188Re-Hepama-1组肿瘤组织放射性摄取为11.53%ID/g,静脉注射188Re-Hepama-1组为2.79%ID/g;而瘤内注射188Re-Hepama-1组血、肝、肾等组织摄取均＜1.00%ID/g,明显低于静脉注射188R-Hepama-I组(均＞1.50%ID/g);静脉注射188Re-Hepama-1组和瘤内注射188Re-Hepama-1组的肿瘤体积与188ReO4-组及188Re-mIgG组的差异均具有统计学意义(P均＜0.05).形态学观察可见瘤内注射188Re-Hepama-1组和静脉注射188Re-Hepama-1组细胞凋亡,凋亡小体及变性坏死增多,而其余组少见.结论 静脉注射和瘤体内注射188Re-Hepama-1对裸鼠模型肝癌具有较好的治疗效应.静脉注射188Re-Hepama-1在临床肝癌的导向治疗方面有较好的应用前景.

Treatment of hepatocellular carcinoma with 188Re-Hepama-1 monoclonal antibody in nude mice

Objective The tissue distribution and tumor suppression of 188Re labeled monoelonal antibody Hepama-1 were studied in nude mice models with hepatocellular carcinoma(HCC).Methods HCC line SMMC-7721 was transplanted into 40 nude mice equally divided into 5 groups:intratumoral 188ReO4-(GB),intratumoral 188Re-mIgG(GC),intravenous 188Re-Hepama-1(GD)and intratumoral 188Re-Hepama-1(GE)treatment,and a control group(GA)with saline.After48 h,3 mice from each group were sacrificed to assess the biodistribution.At the 1st,2nd,3rd and 4th week after treatment,the tumor volume in each group was measured.Three mice from each group were sacrificed after the 4th week measurement to investigate the micro structural and pathological changes.Results The labeling rate of 188Re-Hepama-1 was 85%,and the radiochemical purity was more than 95%.The tumor uptakes(percentage activity of injection dose per gram of tissue,%ID/g)of 188Re-Hepama-1 in GE and GD at 48 h after intratumoral or in travenous administration were 11.53% ID/g and 2.79% ID/g,respectively,which were significantly higher than other groups(P＜0.05).The tumor volume in GE and GD was smaller than in other groups.The morphological changes of nuclear chromatin,apoptotic bodies and cell necrosis were significantly more obvious in the two 188Re-Hepama-1 treated groups.Conclusions 188Re-Hepama-1 treatment is effective in nude mice model of HCC.It might have potential role on the targeting treatment of human HCC.