Design and Optimization of Coin-Shaped Microreactor Chips for PET Radiopharmaceutical Synthesis

• Published in: Journal of Nuclear Medicine Vol. 51; no. 2; pp. 282 - 287
• Main Authors: Elizarov, Arkadij M, van Dam, R. Michael, Shin, Young Shik, Kolb, Hartmuth C, Padgett, Henry C, Stout, David, Shu, Jenny, Huang, Jiang, Daridon, Antoine, Heath, James R
• Format: Journal Article
• Language: English
• Published: United States Soc Nuclear Med 01.02.2010; Society of Nuclear Medicine
• Subjects: Advantages; Animals; Biomarkers; Chemical compounds; Chromatography, Ion Exchange - instrumentation; Design; Elastomers; Equipment Design; Fluorides; Fluorine Radioisotopes; Fluorodeoxyglucose F18 - chemical synthesis; Heat transfer; Humans; Mice; Microfluidic Analytical Techniques - instrumentation; Positron-Emission Tomography; Radiopharmaceuticals - chemical synthesis; Rhabdomyosarcoma - diagnostic imaging
• ISSN: 0161-5505; 1535-5667; 1535-5667; 2159-662X
• DOI: 10.2967/jnumed.109.065946

An integrated elastomeric microfluidic device, with a footprint the size of a postage stamp, has been designed and optimized for multistep radiosynthesis of PET tracers. The unique architecture of the device is centered around a 5-microL coin-shaped reactor, which yields reaction efficiency and speed from a combination of high reagent concentration, pressurized reactions, and rapid heat and mass transfer. Its novel features facilitate mixing, solvent exchange, and product collection. New mixing mechanisms assisted by vacuum, pressure, and chemical reactions are exploited. The architecture of the reported reactor is the first that has allowed batch-mode microfluidic devices to produce radiopharmaceuticals of sufficient quality and quantity to be validated by in vivo imaging. The reactor has the potential to produce multiple human doses of (18)F-FDG; the most impact, however, is expected in the synthesis of PET radiopharmaceuticals that can be made only with low yields by currently available equipment.