固体靶PET核素89Zr的制备、质量控制和抗体标记  

Production and purification of solid target PET nuclide 89Zr and its antibody labeling

作　　者：王风[1] 郭晓轶 刘特立 丁立新 夏雷 丁缙 孟祥溪 蒋金泉 朱华[1] 杨志[1] Wang Feng;Guo Xiaoyi;Liu Teli;Ding Lixin;Xia Lei;Ding Jin;Meng Xiangxi;Jiang Jinquan;Zhu Hua;Yang Zhi(Key laboratory of Carcinogenesis and Translational Research(Ministry of Education),Department of Nuclear Medicine,Peking University Cancer Hospital&Institute,Beijing 100036,China)

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所核医学科、恶性肿瘤发病机制及转化研究教育部重点实验室,100036

出　　处：《中华核医学与分子影像杂志》2020年第5期294-297,共4页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：北京市自然科学基金(7184195);京津冀基础研究合作专项(H2018206600)。

摘　　要：目的进行固体靶PET核素89Zr的制备和质量控制,制备89Zr并标记产物89Zr-去铁胺(DFO)-曲妥珠单克隆抗体(Trastuzumab)。方法采用核反应89Y(p,n)89Zr生产89Zr,设计加工89Y靶的固定靶托,由医用回旋加速器20μA质子束流约12.5 MeV轰击89Y靶约1~2 h。使用羟肟酸树脂分离纯化轰击后的靶片,用1 mol/L草酸溶液淋洗获得89Zr。分析其特征峰、放射性核素纯度及放化纯等。利用89Zr草酸溶液和DFO-Trastuzumab在室温下标记制得89Zr-DFO-Trastuzumab,测定其放化纯。结果成功进行11次89Zr的生产,获得的89Zr产量为555~1506 MBq,产额(34.8±5.2)MBq·μA-1·h-1,获得纯化后产品227.2~991.6 MBq(纯化率42%~87%),产品放射性浓度可达1.0×106 MBq/L。γ能谱分析显示了89Zr的特征峰(511和909 keV),未发现其他杂质峰,放射性核素纯度与放化纯均接近100%。合成的89Zr-DFO-Trastuzumab放化纯>95%,人血清白蛋白(HSA)溶液中放置72 h放化纯仍超过90%。结论通过自行设计靶片,成功制得性能优良的固体靶PET核素89Zr并行抗体标记,为89Zr药物的临床应用提供保障。Objective To produce the solid target nuclide 89Zr,and prepare the probe 89Zr-desferrioxamine(DFO)-Trastuzumab.Methods The 89Y(p,n)89Zr nuclear reaction was used for 89Zr production.89Y target was irradiated by 20μA proton in a medical cyclotron(E=12.5 MeV)for about 1-2 h.89Zr was purified from hydroxamate resin using 1 mol/L oxalic acid solution.The characteristic peak,radionuclide purity and radiochemical purity of 89Zr were determined byγ-ray spectroscopy.89Zr-DFO-Trastuzumab probe was synthesized by the reaction of 89Zr-oxalate and DFO-Trastuzumab at room temperature,and the radiochemical purity was measured.Results 89Zr was prepared successfully for 11 times,and the production of 89Zr was 555-1506 MBq,with production rate of(34.8±5.2)MBq·μA-1·h-1.After the purification(purification rate:42%-87%),227.2-991.6 MBq 89Zr was obtained,with the concentration of 1.0×106 MBq/L.Theγspectrum showed that the characteristic peak of 89Zr were 511 and 909 keV,and no impurities were found.The radionuclide purity and radiochemical purity were both close to 100%.89Zr-DFO-Trastuzumab was successfully labeled with radiochemical purity more than 95%,and it was above 90%within 72 h in human serum albumin(HSA)solution.Conclusion Through the self-designed target assembling,the solid target PET nuclide 89Zr with high quality and labeling are successfully achieved,which provides guarantee for the clinical application of the 89Zr drug.

关 键 词：锆 放射性同位素 同位素标记 去铁胺 抗体 单克隆 

分 类 号：R[医药卫生]