64Cu标记DKFZ-PSMA-617探针的制备、质控及体内分布的研究

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。

Preparation,Quality Control and Biodistribution Analysis of64Cu Labeled DKFZ-PSMA-617 and its Clinical Translation Research

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 of⁶⁴Cu-PSMA-617 were established. Methods:⁶⁴Ni (p, n)⁶⁴Cu nuclear reaction was applied for the production of⁶⁴Cu. The labeling conditions were optimized to achieve rapid labeling process and high purity of⁶⁴Cu-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 of⁶⁴Cu-PSMA-617. Referring to the 2015 Chinese pharmacopoeia standard, the preliminary quality control of⁶⁴Cu-PSMA-617 was carried out. The bio-distribution of the probe was evaluated by intravenous injection of 1.85 MBq⁶⁴Cu-PSMA-617 to Balb/c mice. Results: The labeled yield of⁶⁴Cu-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 formulate⁶⁴Cu-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.