【摘要】 目的死亡受体5(death receptor 5,DR5)单克隆抗体zaptuzumab可以激活DR5,特异地引起肿瘤细胞的凋亡。zaptuzumab体内结合肿瘤细胞的显像研究有助于了解DR5的分布和zaptuzumab靶向肿瘤的性能。方法本研究采用琥珀酰-联肼尼克酰胺(Hynic,succinimidyl 6-hydrazinonicotinate)法在zaptuzumab上标记99mTc;薄层层析法分析标记效率;排阻层析纯化99mTc-zaptuzumab;酶联免疫吸附法(enzyme-linked immunosorbent assay,ELISA)测定99mTc-zaptuzumab的结合活性;用裸鼠皮下接种H460肺癌模型结合平面显像分析99mTc-zaptuzumab对肺癌的靶向性能。结果99mTc标记zaptuzumab效率达到50%以上,纯化后99mTc-zaptuzumab的纯度达到95%以上;ELISA结果显示标记抗体保持了大部分和DR5的结合活性;平面显像显示尾静脉注射后1.5、4.5h99mTc-zaptuzumab在H460肺癌内摄取较低。结论99mTc-zaptuzumab用Hynic法标记取得成功,抗原结合活性基本保持,但99mTc-zaptuzumab对H460肺癌靶向效果不佳。更多还原

【Abstract】 Objective Death receptor 5(DR5) monoclonal antibody zaptuzumab can activate DR5 resulting in specific apoptosis of tumor cells.The imaging of zaptuzuma with binding activity to tumor cells is helpful to identify the bio-distribution of death receptor in vivo and characterize the tumor-targeting property of zaptuzumab.Methods Zaptuzumab was labeled with 99mTc by Hynic(succinimidyl 6-hydrazinonicotinate) method.The labeling yield was determined by instant thin-layer chromatography.99mTc-zaptuzumab was purified by size exclusion chromatography.The binding activity of 99mTc-zaptuzumab to DR5 was tested by enzyme-linked immunosorbent assay(ELISA).The planar imaging in subcutaneously implanted H460 lung cancer models was carried out to characterize the lung cancer-targeting property of 99mTc-zaptuzumab.Results The labeling yield of 99mTc-zaptuzumab was above 50%.The radiochemical purity of 99mTc-zaptuzumab after purification was above 95%.ELISA data indicated that the binding activity of 99mTc-zaptuzumab was largely retained.Planar imaging indicated that the accumulation of v99mTc-zaptuzumab in H460 xenograft at 1.5,4.5h time-points after administration was relatively low.Conclusion The labeling of v99mTc-zaptuzumab by Hynic method was successful and the antigen-binding activity of 99mTc-zaptuzumab was retained.However,the targeting property of v99mTc-zaptuzumab to H460 lung cancer was poor.更多还原