title: Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics.
abstract: 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.
authors.affiliation: Department of Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Chung-Cheng
authors.initials: CC
authors.lastname: Lee
authors.forename: Guodong
authors.initials: G
authors.lastname: Sui
authors.forename: Arkadij
authors.initials: A
authors.lastname: Elizarov
authors.forename: Chengyi Jenny
authors.initials: CJ
authors.lastname: Shu
authors.forename: Young-Shik
authors.initials: YS
authors.lastname: Shin
authors.forename: Alek N
authors.initials: AN
authors.lastname: Dooley
authors.forename: Jiang
authors.initials: J
authors.lastname: Huang
authors.forename: Antoine
authors.initials: A
authors.lastname: Daridon
authors.forename: Paul
authors.initials: P
authors.lastname: Wyatt
authors.forename: David
authors.initials: D
authors.lastname: Stout
authors.forename: Hartmuth C
authors.initials: HC
authors.lastname: Kolb
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: James R
authors.initials: JR
authors.lastname: Heath
authors.forename: Michael E
authors.initials: ME
authors.lastname: Phelps
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Quake
authors.forename: Hsian-Rong
authors.initials: HR
authors.lastname: Tseng
mesh_terms: D000818:Animals; D001331:Automation; D005459:Fluorides; D019788:Fluorodeoxyglucose F18 / Q000138:chemical synthesis*; D008401:Gas Chromatography-Mass Spectrometry; D051379:Mice; D044085:Microfluidics; D008904:Miniaturization; D015335:Molecular Probes / Q000138:chemical synthesis*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging; D012997:Solvents; D014055:Tomography, Emission-Computed
chemical_list: D015335:Molecular Probes; D019275:Radiopharmaceuticals; D012997:Solvents; D019788:Fluorodeoxyglucose F18; D005459:Fluorides