Design and optimization of coin-shaped microreactor chips for PET radiopharmaceutical synthesis.
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Elizarov
Arkadij M
AM
Siemens Molecular Imaging, Biomarker Research, Culver City, California 90230, USA. arkadij.elizarov@siemens.com
van Dam
R Michael
RM
Shin
Young Shik
YS
Kolb
Hartmuth C
HC
Padgett
Henry C
HC
Stout
David
D
Shu
Jenny
J
Huang
Jiang
J
Daridon
Antoine
A
Heath
James R
JR
D000818:Animals; D002852:Chromatography, Ion Exchange / Q000295:instrumentation; D020724:Elastomers; D004867:Equipment Design; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18 / Q000138:chemical synthesis; D006801:Humans; D051379:Mice; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging
D020724:Elastomers; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18