人肝细胞癌转铁蛋白受体显像及靶向治疗研究

Study of transferrin receptor imaging and targeting radioimmunotherapy of human hepatocellular carcinoma.

目的探讨131I-D2C5用于肿瘤受体成像和放射免疫治疗的价值。方法人肝细胞癌SMMC-7721采用隧道包埋法植入Balb/c(-/-)裸鼠肝左叶,建立原位种植肿瘤模型。①12只荷瘤裸鼠随机分为两组,每组6只,分别经尾静脉注射131I-D2C51、31I-mIgG,放射剂量均为14.8MBq/只;SPECT采集131I-D2C5和131I-mIgG注射后6h、24h放射自显影图像;γ计数器检测体内放射性分布。②18只荷瘤裸鼠随机分为两组,每组9只,每周分别经腹腔注射131I-D2C51、31I-mIgG,连续6周;另外9只荷瘤裸鼠每周腹腔注射生理盐水200μl作为对照组。8周后比较各组肿瘤体积,计算其生长抑制率,评估肿瘤坏死程度。结果注射131I-D2C5后6h时,裸鼠肝肿瘤部位显影,24h时肿瘤显影最清晰。注射131I-mIgG后,肿瘤部位未见明显放射性浓聚。24h时131I-D2C5组裸鼠体内肿瘤/血为6.6,肿瘤/肝为2.2,肿瘤/肌肉为20.8。静脉注射131I-D2C5导向治疗较131I-mIgG更显著抑制人肝细胞癌裸鼠模型中肿瘤的生长,促进肿瘤坏死。结论131I-D2C5能与人肝细胞癌SMMC-7721高特异性、高亲和力地结合。在肝癌显像及生物靶向治疗中具有广泛的应用前景。

Objective To evaluate the effect of tumor receptor imaging and radioimmunotherapy with ^131I-D2C5 in nude mice bearing human hepatocellular carcinoma SMMC-7721. Methods Human hepatocellular carcinoma cells SMMC-7721 was transplanted into the left lobe of the liver of Balb/c （ - / - ） nude mice to establish a hepatoma model. OTwelve nude mice bearing SMMC-7721 were randomized into 2 groups （n = 6） to receive intravenous injection of ^131I-D2C5 and ^131I-mIgG via caudal vein, respectively, all at the equivalent dose of 14. 8MBq. Autoradiogram of ^131I-D2C5 and ^131I-mIgG in nude mice bearing SMMC-7721 xenografts were investigated 6h, 24h after injection by SPECT. All mice were sacrificed after imaging for biodistribution observation by γ counter technologies. QEighteen nude mice were randomized into two groups（n= 9） to received intraperitoneal injection of ^131I-D2C5 and ^131I-mIgG, once a week for six weeks. Another 9 tumor-bearing mice received only intravenous injection of 200μl normal saline as the control group. Tumor volume changes were monitored after 8 weeks and tumor growth inhibiting rates were calculated. Degree of necrosis in tumors was evaluated. Results Hepatoma in nude mice were visible at 6h and became distinct at 24h post injection of ^131I-D2C5 , while there was no special radioactivity concentration in tumor after injection of ^131I-mIgG. At 24h post injection, the ratios of tumor/blood, tumor/liver and tumor/muscle were 6.6, 2. 2 and 20. 8, respectively. ^131I-D2C5 Caused greater inhibition of tumor growth and increase the degree of necrosis in tumor than ^131I- mIgG as compared to the control group. Conclusion ^131I-D2C5 has good specificity and high affinity of binding to human hepa- tocellular carcinoma tissues SMMC-7721. It may be used in the targeting diagnosis and therapy of liver cancer.