B7-H3单克隆抗体4H7的131I标记方法及体内生物分布

The preparation and biological evaluation of 131I labeling anti-B7-H3 monoclonal antibody 4H7

目的 探讨鼠抗人B7-H3单克隆抗体4H7的131I标记方法,观察标记抗体药代动力学特点及其在肾癌皮下移植瘤模型中生物学分布与显像.方法 采用氯胺T法进行标记,测定131I-4H7标记率、放化纯和稳定性.对131I-4H7体内分布及药物代谢动力学进行研究.观察131I-4H7在荷肾透明细胞癌（786-0细胞）裸鼠皮下移植瘤模型中的生物学分布,并进行单光子发射计算机断层（SPECT）显像研究.结果 131I-4H7标记率为61.64％,放化纯为98.4％.131I-4H7在美国癌症研究所小鼠（ICR小鼠）体内代谢过程符合一级血药动力学二室模型,快相清除半衰期（t1/2α）为27.94 min,慢相清除半衰期（t1/2β）为1 634.74 min,在体内主要通过肝脏和肾脏代谢.荷瘤小鼠实验研究中显示131I-4H7在肿瘤组织中停留时间较长,且皮下移植瘤摄取率较高,在24h达最高,为3.15％ID/g.荷瘤鼠体内SPECT显像研究显示,131I-4H7组在各个时间点放射浓聚高于Na131I组.结论 131I-4H7易于制备,放化纯度高,标志物的稳定性好,可以达到实验要求.131I-4H7在肾癌荷瘤鼠中具有较高的摄取率和较长的滞留时间,具有良好的靶向性.

Objective To assess the radiobiological effect of 131I labeled recombinant human B7-H3 monoclonal antibody （131I-4H7） in nude mice with human renal cell carcinoma （RCC）.Methods Chloramine-T method was used for 131I labeling 4H7.Labeling efficiency,radiochemical purity and stability were estimated by using paper chromatography method.The activity and tumor uptake of 131I-4H7 were measured by tissue distribution assay and single-photon emission computed tomography （SPECT） imaging after injection of 131I-4H7.Results The labeling efficiency and radiochemical purity of 131I-4H7 were 61.64％ and 98.4％,respectively.The in vivo distribution and elimination of 131I-4H7 were consistent with a first-order and two-compartment model,t1/2α =27.94 min,t1/2β =1634.74 min.The metabolism of 131I-4H7 mainly depended on liver and kidney.The tissue distribution assay and SPECT imaging showed that 131I-4H7 was markedly absorbed by the tumor and reached its maximal uptake rate （3.15％ ID/g） at 24 hours.Compared with the Na131I group,the 131I-4H7 group showed higher uptake of 131I at each time point.Conclusion The labeling rate and radiochemical purity of 131I-4H7 is high,simple and the stability of 131I-4H7 is fine.