Crump Institute for Molecular Imaging, University of California Los Angeles, Los Angeles, CA, USA.
Department of Molecular & Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA.
Methods Mol Biol. 2022;2393:813-828. doi: 10.1007/978-1-0716-1803-5_43.
The short-lived radiolabeled "tracers" needed for performing whole body imaging in animals or patients with positron-emission tomography (PET) are generally produced via automated "radiosynthesizers". Most current radiosynthesizers are designed for routine production of relatively large clinical batches and are very wasteful when only a small batch of a tracer is needed, such as is the case for preclinical in vivo PET imaging studies. To overcome the prohibitively high cost of producing small batches of PET tracers, we developed a droplet microreactor system that performs radiochemistry at the 1-10μL scale instead of the milliliter scale of conventional technologies. The overall yield for the droplet-based production of many PET tracers is comparable to conventional approaches, but 10-100× less reagents are consumed, the synthesis can be completed in much less time (<30 min), and only a small laboratory footprint and minimal radiation shielding are needed. By combining these advantages, droplet microreactors enable the economical production of small batches PET tracers on demand. Here, we describe the fabrication method of the droplet microreactor and the droplet-based synthesis of an example radiotracer ([F]fallypride).
用于正电子发射断层扫描（PET）动物或患者全身成像的短寿命放射性标记“示踪剂”通常通过自动化“放射性合成器”来生产。大多数当前的放射性合成器旨在用于相对较大的临床批次的常规生产，而当仅需要少量示踪剂批次时，例如在临床前体内 PET 成像研究中，就会非常浪费。为了克服生产少量 PET 示踪剂的高成本，我们开发了一种液滴微反应器系统，该系统可在 1-10μL 范围内进行放射化学，而不是传统技术的毫升范围。基于液滴的许多 PET 示踪剂的生产的总产率与传统方法相当，但消耗的试剂少 10-100 倍，合成时间大大缩短（<30 分钟），并且只需要很小的实验室占地面积和最小的辐射屏蔽。通过结合这些优势，液滴微反应器可按需实现经济的小批量 PET 示踪剂生产。在这里，我们描述了液滴微反应器的制造方法以及示例放射性示踪剂([F]fallypride)的基于液滴的合成方法。
