Microreactors for radiopharmaceutical discovery
and manufacturing
R. Michael van Dam
Crump Institute for Molecular Imaging, University of California Los Angeles
Professor
Compared to the manufacturing of conventional pharmaceuticals, the preparation of a radiolabeled compound for diagnostic imaging (e.g. using positron-emission tomography; PET) or targeted radiotherapy poses a number of unique challenges. Automation and heavy lead shielding are required for radiation protection, and the short half-life of the radionuclide requires a whole network of geographically distributed network of production facilities, combined with tight scheduling among the patient, medical facility, production site, and transportation services, to ensure an available supply of the radiopharmaceutical around the world. The high costs and complexity of current radiopharmaceutical manufacturing technologies makes the compounds very expensive, and there have been extensive efforts to innovate how radiochemistry is performed to alleviate these issues.
This talk will illustrate the fundamental challenges encountered in radiosynthesis and analysis and review how various microfluidic and miniaturization technologies have been applied in the field, including flow-based approaches and batch microreactors. I will describe in particular our new approach based on droplet microreactors, in which reactions are performed at 100x smaller volume scale than conventional instruments. The reduced volume enables dramatic improvements in yield, synthesis time, reagent consumption, specific activity and cost, and by concentrating radionuclides into microscale volumes, the quantity of radiopharmaceutical product of these systems can be scaled anywhere from small preclinical batches up to larger scale multi-patient-dose batches. The compact size could enable the transformation of today’s costly radiopharmacies into benchtop devices, facilitating vast improvements in cost and availability of these specialized compounds.
Moreover, microfluidic systems can be leveraged as a platform for serial or parallel high-throughput experimentation, providing an unprecedented level of throughput compared to conventional radiochemistry apparatus. When coupled with high-throughput analysis methods, such systems can accelerate synthesis optimization, or screening substrate scope of new synthesis routes, reducing experimental timescales from months to weeks.
Full automation of the economical and time-efficient techniques are around the corner, and they could have significant impacts on how radiopharmaceutical research is performed, and how radiopharmaceuticals are manufactured and distributed to investigators and patients.