摘要
目的研发批型^18F正电子药物微流体合成器自动化控制系统，并合成18F-脱氧葡萄糖（FDG）。方法微流体合成器的微管道部分利用丝印技术和聚二甲基硅氧烷（PDMS）材料制作，微反应瓶使用定制的具有加热和冷却功能的玻璃瓶制成。利用可编程逻辑控制器、微气阀、温度传感器、恒压气源、稳压电源及负压泵实现对合成器数字量部分和模拟量部分的控制，人机交互界面基于Kingview软件设计。通过编写合成^18F-FDG的程序并自动化多次合成18F-FDG来测试系统的稳定性及可靠性，测定合成的^18F-FDG的标记率、放化纯、氨基聚醚（K2.2.2）含量、乙腈残余量、产品性状、pH值，并对产品进行无菌检查和细菌内毒素检查。结果制成的^18F批型微流体合成器大小为10 cm×10 cm×15 cm，其控制系统大小类似于台式机机箱，单次合成^18F-FDG使用的前体量为2.5 mg。控制系统人机交互界面能够让用户自主编程，利用该控制系统合成的^18F-FDG放化纯大于95%，第1步^18F标记反应的标记率为（92.4±1.4）%。^18F-FDG产率为（35.6±5.6）%（时间校正）,乙腈含量为（12.8±2.6） μg/g, K2.2.2含量均低于50 μg/g,无菌检查和细菌内毒素检查结果均为阴性，产品性状为澄明液体，pH值为6.2±0.4。结论成功制备了批型18F正电子药物微流体合成器，并进行了^18F-FDG的合成。该合成器具有集成度高、体积小、标记前体用量少、易编程等优点。
ObjectiveTo develop an automated control system of batch-reactor microfluidic device for the synthesis of PET tracers and to use it for the preparation of ^18F-fluorodeoxyglucose （FDG）.MethodsThe 18F microreactor was composed of polydimethylsiloxane （PDMS） microfluidic chip and customized glass microvessel integrated with stainless capillary tube as heater or cooler. PDMS chip was fabricated by silk-screen printing technology. The hardware control of digital and analog quantity of synthesizer was completed by organic integration programmable logic controller （PLC）, micro air valve, temperature sensor, compressed air source, direct current stabilized voltage source and vacuum pumps. The interface was designed using Kingview software. Thin-layer chromatography （TLC） was applied to measure the ^18F-labeling yield and the radiochemical purity of ^18F-FDG. Kryptofix （K2.2.2） content, residual acetonitrile content, traits, aseptic and bacterial endotoxins levels were also tested.ResultsThe size of the microfluidic device was 10 cm×10 cm×15 cm. The size of the automated control system was similar to the desktop chassis. The amount of precursor used in the single synthesis of ^18F-FDG was 2.5 mg. The radiochemical purity of ^18F-FDG was higher than 95%, the labeling yield was （92.4±1.4）% and the ^18F-FDG yield was （35.6±5.6）%（decay corrected）. The ^18F-FDG product was clear and colorless, and the pH value was 6.2±0.4. The K2.2.2 content was less than 50 μg/g. The residual acetonitrile content was （12.8±2.6） μg/g. Both aseptic and bacterial endotoxins tests were negative.ConclusionsA batch-mode microfluidic device is developed and successfully applied to prepare ^18F-FDG. It has the advantages of high integration, small size, less consumption of labeling precursor and easy programming.
作者
张建平
王明伟
章英剑
张勇平
Zhang Jianping;Wang Mingwei;Zhang Yingjian;Zhang Yongping(Department of Nuclear Medicine, Fudan University Shanghai Cancer Cente;Department of Oncology, Shanghai Medical College, Fudan Universit;Center for Biomedical Imaging, Fudan Universit;Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai 200032, Chin)
出处
《中华核医学与分子影像杂志》
CAS
北大核心
2018年第5期345-350,共6页
Chinese Journal of Nuclear Medicine and Molecular Imaging
基金
上海市科学技术委员会科研计划项目（14DZ2251400）
复旦大学附属肿瘤医院院级课题（YJ201412）
