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

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.