Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics

Chung-Cheng Lee, Guodong Sui, Arkadij Elizarov, Chengyi Jenny Shu, Young-Shik Shin, Alek N Dooley, Jiang Huang, Antoine Daridon, Paul Wyatt, David Stout, Hartmuth C Kolb, Owen N Witte, Nagichettiar Satyamurthy, James R Heath, Michael E Phelps, Stephen R Quake, Hsian-Rong Tseng
Science 2005 December 16, 310 (5755): 1793-6
Microreactor technology has shown potential for optimizing synthetic efficiency, particularly in preparing sensitive compounds. We achieved the synthesis of an [(18)F]fluoride-radiolabeled molecular imaging probe, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), in an integrated microfluidic device. Five sequential processes-[18F]fluoride concentration, water evaporation, radiofluorination, solvent exchange, and hydrolytic deprotection-proceeded with high radio-chemical yield and purity and with shorter synthesis time relative to conventional automated synthesis. Multiple doses of [18F]FDG for positron emission tomography imaging studies in mice were prepared. These results, which constitute a proof of principle for automated multistep syntheses at the nanogram to microgram scale, could be generalized to a range of radiolabeled substrates.

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