^(99)Tc^m-Herceptin的放射性标记与显像研究

Study on Radiolabelling and imaging of ^(99)Tc^m-Herceptin

目的探索HER2阳性胃癌显像剂99Tcm-Herceptin的标记方法,并进行荷瘤动物模型的显像研究。方法分别采用2-巯基乙醇(2-mercaptoethanol,2-ME)法和2-亚氨基噻吩(2-iminothiolane,2-IT)法标记赫赛汀(Herceptin)。评价不同标记方法对抗体活性和标记率的影响。通过高效液相色谱(high performance liquid chromatography,HPLC)测定标记抗体99Tcm-2-IT-Herceptin的体外稳定性。建立HER2阳性胃癌动物模型,并进行显像研究。结果 2-IT法标记Herceptin具有较高的标记率(>95%),且不会破坏抗体的完整性。标记抗体具有较高的体外稳定性。荷瘤动物模型注射99Tcm-2-IT-Herceptin 24h后,可以得到清晰的肿瘤显像结果。结论 99Tcm-2-IT-Herceptin具有较高的标记效率和体外稳定性,对所采用的HER2阳性动物模型具有靶向性,可能进一步开发成为新型HER2阳性胃癌显像剂。

Objective To explore the radiolabelling methods on HER2 positive gastric cancer agent ^99Tc^m-Her- eeptin, and to investigate the imaging of ^99Tc^m-Herceptin on tumor-bearing animal model. Methods Herceptin was labeled with 99Tcm through 2-mercaptoethanol and 2-iminothiolane, respectively. The antibody＇s biological activity and labeling yields were evaluated. The stability of ^99Tc^m-2-IT-Hereeptin was determined by HPLC in vitro. Animal models that were borne HER2 positive gastric tumors were set u Pfor imaging study. Results The Herceptin labeled through 2-iminothiolane showed high labeling yields （ 〉 95 % ） and antibody integrity. The 99Tcm-2-IT-Hereeptin had high stability in vitro. The clear imaging of ^99Tc^m-2-IT-Herceptin in tumor-bearing animal model 24h post-injection was obtained. Conclusion High labelling yield and stability in vitro were achieved for ^99Tc^m-2-IT-Herceptin, and it may potentially be used as a novel agent for HER2 positive gastric cancer imaging.