Molecular Imaging Biomarker Research, Siemens Healthcare, 6100 Bristol Pkw, Culver City, California, USA.
Lab Chip. 2013 Jan 7;13(1):136-45. doi: 10.1039/c2lc40853h. Epub 2012 Nov 7.
The very first microfluidic device used for the production of (18)F-labeled tracers for clinical research is reported along with the first human Positron Emission Tomography scan obtained with a microfluidically produced radiotracer. The system integrates all operations necessary for the transformation of [(18)F]fluoride in irradiated cyclotron target water to a dose of radiopharmaceutical suitable for use in clinical research. The key microfluidic technologies developed for the device are a fluoride concentration system and a microfluidic batch reactor assembly. Concentration of fluoride was achieved by means of absorption of the fluoride anion on a micro ion-exchange column (5 μL of resin) followed by release of the radioactivity with 45 μL of the release solution (95 ± 3% overall efficiency). The reactor assembly includes an injection-molded reactor chip and a transparent machined lid press-fitted together. The resulting 50 μL cavity has a unique shape designed to minimize losses of liquid during reactor filling and liquid evaporation. The cavity has 8 ports for gases and liquids, each equipped with a 2-way on-chip mechanical valve rated for pressure up to 20.68 bar (300 psi). The temperature is controlled by a thermoelectric heater capable of heating the reactor up to 180 °C from RT in 150 s. A camera captures live video of the processes in the reactor. HPLC-based purification and reformulation units are also integrated in the device. The system is based on "split-box architecture", with reagents loaded from outside of the radiation shielding. It can be installed either in a standard hot cell, or as a self-shielded unit. Along with a high level of integration and automation, split-box architecture allowed for multiple production runs without the user being exposed to radiation fields. The system was used to support clinical trials of [(18)F]fallypride, a neuroimaging radiopharmaceutical under IND Application #109,880.
报告了第一个用于临床研究的（18）F 标记示踪剂生产的微流控设备，以及使用微流控生产的放射性示踪剂获得的第一个人类正电子发射断层扫描 (PET) 扫描。该系统集成了将辐照回旋加速器靶水中的 [(18)F] 氟化物转化为适合临床研究使用的放射性药物所需的所有操作。为该设备开发的关键微流控技术是氟化物浓缩系统和微流批反应器组件。氟化物的浓缩是通过将氟阴离子吸收在微离子交换柱（5 μL 树脂）上来实现的，然后用 45 μL 释放溶液释放放射性（总效率为 95 ± 3%）。反应器组件包括注塑成型的反应器芯片和透明加工的盖子，压配合在一起。由此产生的 50 μL 腔具有独特的形状，旨在最大限度地减少填充和液体蒸发过程中液体的损失。该腔有 8 个用于气体和液体的端口，每个端口都配备了一个双通道的片上机械阀，可承受高达 20.68 巴（300 psi）的压力。温度由热电加热器控制，该加热器可在 150 秒内将反应器从室温加热至 180°C。一个摄像头捕捉反应器中过程的实时视频。基于 HPLC 的纯化和再配方单元也集成在设备中。该系统基于“分体盒架构”，试剂从辐射屏蔽外加载。它可以安装在标准热室中，也可以作为自屏蔽单元。分体盒架构除了具有高度的集成度和自动化程度外，还允许在不使使用者暴露于辐射场的情况下进行多次生产运行。该系统用于支持 IND 申请 #109,880 下的神经成像放射性药物 [(18)F] 氟拉培德的临床试验。
