转位蛋白特异性显像剂18F-DPA-714的在线自动化合成及其质量控制

Automatic synthesis and quality control of translocation protein specific imaging agent 18 F-DPA-714

目的建立^(18)F-DPA-714的在线自动化合成方法及其质量控制方法。方法采用日本住友CFN-F100多功能合成模块,自主编辑自动化合成程序,回旋加速器HM-10生产出来的18F-经QMA柱捕获,洗脱,干燥除水后,与前体进行亲核取代反应。粗产品转移至半制备型高效液相色谱(HPLC)分离纯化,收集产品峰,加水稀释后,转移至C_(18)柱上,再经水洗,最后用2mL乙醇洗脱,加生理盐水稀释,经无菌滤膜过滤得到产品。测定其pH值、放射化学纯度、稳定性及细菌内毒素等。结果在线自动化制备^(18)F-DPA-714放射化学纯度>99%,未衰减校正的合成效率为18%~36%(n=20),比活度可达675GBq/mg,整个制备时间约为55min。结论该18F-DPA-714在线自动化制备方法简单,易于操作,工艺安全,有利于工作人员的辐射防护,合成效率稳定,放射化学纯度高,比活度高,各项指标合格,满足临床使用需求。

Objective To establish the automatic synthesis method and quality control method of ^(18)F-DPA-714.Methods Using Sumitomo CFN-F100 multifunctional synthesis module in Japan,the automatic synthesis program was edited independently.^(18)F-produced by cyclotron HM-10 was captured by QMA column,then eluted,dried and dewatered,and nucleophilic substitution reaction was carried out with the precursor.The crude product was transferred to semi-preparative high-performance liquid chromatography(HPLC)for separation and purification,the peak of the product was collected,diluted with water,transferred to the C_(18) column,then washed with water,and finally eluted with 2 mL ethanol,diluted with normal saline,and obtained the product through the sterile filter membrane.The pH value,radiochemical purity,stability and bacterial endotoxin were measured.Results Online automatic preparation of ^(18)F-DPA-714 radiochemical purity was>99%,and synthesis efficiency without attenuation correction was 18%-36%(n=20),the specific activity could reach 675 GBq/mg,and the entire preparation time was about 55 min.Conclusion The online automatic preparation method of ^(18)F-DPA-714 is simple,easy to operate,safe,favorable for radiation protection of workers,stable in synthesis efficiency,high in radiochemical purity,high in specific activity,and qualified in various indexes,which can meet the needs of clinical use.