64Cu标记DKFZ-PSMA-617探针的制备、质控及体内分布的研究  

Preparation, Quality Control and Biodistribution Analysis of 64Cu Labeled DKFZ-PSMA-617 and its Clinical Translation Research

作　　者：朱华[1] 刘特立 王风[1] 蒋金泉 韩雪迪 杨志[1] ZHU Hua;LIU Teli;WANG Feng;JIANG Jinquan;HAN Xuedi;YANG Zhi(Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing),Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing 100142, 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

出　　处：《同位素》2019年第6期382-387,I0001,共7页Journal of Isotopes

基　　金：国家自然科学基金(81401467,81371592);北京市科技新星项目(Z171100001117020);北京市卫生局基金项目(215学科骨干,2015-3-072)

摘　　要：目的:利用医用回旋加速器固体靶系统制备PET核素64Cu,进行前列腺特异性膜抗原(PSMA)分子探针DKFZ-PSMA-617(PSMA-617)研究。建立64Cu-PSMA-617标记化合物生产及初步快速质量控制方法,为PSMA高表达肿瘤的PET显像及放射性免疫导向手术提供新型探针。方法:通过优化反应条件,实现固体靶制备的64Cu对PSMA-617的快速标记与纯化。利用放射性薄层层析分析(Radio-thin layer chromatography, Radio-TLC)和放射性高效液相色谱(Radio-high performance liquid chromatography, Radio-HPLC),进行64Cu-PSMA-617放化纯和稳定性检测。参考2015年《中国药典》进行64Cu-PSMA-617的初步质量控制。通过静脉注射1.85 MBq的64Cu-PSMA-617至Balb/c小鼠体内,进行该探针的体内分布研究。结果: 64Cu-PSMA-617的标记率>96%,放化纯度>98%,标记化合物在多种缓冲液中放置24 h依然保持原有放化纯度。经过尾部静脉注射到小鼠体内后,放射性主要积累在肝脏/肾脏部位,符合该探针在生物体内的代谢行为。结论:本研究实现了64Cu-PSMA-617探针的快速标记并建立了其质量控制方法,64Cu-PSMA-617具有较好的理化性质,体内分布研究确认了其具有较好的生物学性质,该研究结果可为其进一步用于前列腺癌诊疗的临床转化奠定基础。Objective: In order to provide a new probe for the PET imaging of the high expression of PSMA related tumors. The production, quality control and bio-distribution of 64Cu-PSMA-617 were established. Methods: 64Ni(p, n) 64Cu nuclear reaction was applied for the production of 64Cu. The labeling conditions were optimized to achieve rapid labeling process and high purity of 64Cu-PSMA-617 formulation. Radio-thin layer chromatography(Radio-TLC) and Radio-high performance liquid chromatography(Radio-HPLC) were used to detect the purity and stability of 64Cu-PSMA-617. Referring to the 2015 Chinese pharmacopoeia standard, the preliminary quality control of 64Cu-PSMA-617 was carried out. The bio-distribution of the probe was evaluated by intravenous injection of 1.85 MBq 64Cu-PSMA-617 to Balb/c mice. Results: The labeled yield of 64Cu-PSMA-617 was over 96%, the radiochemical purity was over 98%, and the tracer remained 24 hours in various buffers. After the injection of the tail vein in mice, bio-distribution studies at 1 hour, 24 hours and 48 hours. 64Cu-PSMA-617 showed that the radioactivity was mainly accumulated in the liver/kidney, which accorded with the metabolic behavior. Conclusion: In this study, 64Cu was rapidly labeled to formulate 64Cu-PSMA-617 tracer. The quality control method was established and validated. 64Cu-PSMA-617 exhibits good radio-chemical properties. Bio-distribution studies confirm that it has good biological properties. It lays the foundation for the further clinical translational study in non-invasive PET imaging of prostate cancer.

关 键 词：PSMA-617 铜-64 前列腺癌 正电子断层显像 

分 类 号：TL923[核科学技术—核燃料循环与材料] R817.9[医药卫生—影像医学与核医学]