Economical Production of Radiopharmaceuticals for Preclinical Imaging Using Microdroplet Radiochemistry.

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 ([