人源化抗肝癌双链抗体纳米颗粒对荷人肝癌裸鼠放射免疫显像研究

摘要

Objective To investigate the radioimmunoimaging of 99mTc labelled humanized single-chain Fv dimmers(BDM3) and immunonanoparticles for hepatocellular carcinoma in nude mice bearing human hepatocellu-lar carcinoma,and to study their application in diagnosis and therapy of hepatocellular carcinoma. Methods The label rate of 99mTc-BDM3 and 99mTc-BDM3 nanoparticles was determined by isotopic analyzer. The labelled BDM3 and BDM3 nanoparticles were injected intraperitoneally into the nude mice bearing human hepatocellular carcino-ma. At intervals of 1 h,4 h and 8 h,the mice in each group were imaged on a SPECT,and then were sacrificed immediately to get various organs and tumors. Radioactivity ratio of tumor to non-tumor (T/NT) was measured. Results The label rates of 99mTc-BDM3 and 99mTc-BDM3 nanoparticle were 91% and 92%,respectively;The posi-tive display rates by the antibody and its nanoparticle were both 100%;The ratio of T/NT were (1.63±0.17) and (3.63±0.21) 1 h,(3.82±0.24) and (5.63±0.26) 4 h,(0.48±0.21) and (1.41±0.32) 8 h after injection of 99mTc-BDM3 and 99mTc-BDM3 nanoparticle,respectively. The differences between two groups were statistical sig-nificance;Favorable images were obtained after 4 h. The labelled BDM3 and BDM3 nanoparticles concentrated in carcinoma and did not in nontumor,that showed an evident targeting effect in tumor. As a result of a double tar-geting effect,the BDM3 nanoparticles group had more concentration in tumor,and increased the imaging effect. Conclusions The humanized single-chain Fv dimmers (BDM3) and immunonanoparticles for hepatocellular car-cinoma has high affinity to nude mice bearing human hepatocellular carcinoma xenografts. They could be target carrier for diagnosis and therapy of hepatocellular carcinoma.%目的：观察99mTc 标记的人源化抗肝癌双链抗体 BDM3及双链抗体纳米颗粒在荷肝癌动物体内的靶向分布及放射免疫显像，探讨其对肝癌的靶向诊断和治疗的价值。方法使用99mTc 对人源化抗肝癌双链抗体 BDM3及双链抗体纳米颗粒进行标记，并测定标记率，将标记好的抗体及抗体纳米颗粒经腹腔注入荷瘤裸鼠体内，在注射后不同时间点进行放射免疫显像。取各脏器及肿瘤组织，计算肿瘤/非肿瘤比值。结果99mTc 标记的双链抗体BDM3和双链抗体纳米颗粒标记率为91%和92%，显像率均达100%。注射后1 h 肿瘤/血比值为（1.63±0.17）和（3.63±0.21），4 h 肿瘤/血比值为（3.82±0.24）和（5.63±0.26），8 h 肿瘤/血比值为（0.48±0.21）和（1.41±0.32），两组比较，差异均有统计学意义（P<0.01，P<0.001和 P<0.01），表明同位素标记的双链抗体和双链抗体纳米颗粒均能在肿瘤组织中浓聚，而在非肿瘤组织中无浓聚现象，因而具有明确的靶向性，而抗体纳米颗粒因具有双重靶向作用，其浓聚现象较抗体本身更显著，能进一步增加显像效果。结论99mTc 标记的双链抗体 BDM3及其纳米颗粒对肝癌组织具有很好的亲和力，可作为肝癌诊断和治疗的靶向载体。