Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics.
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.
Lee
Chung-Cheng
CC
Department of Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA.
Sui
Guodong
G
Elizarov
Arkadij
A
Shu
Chengyi Jenny
CJ
Shin
Young-Shik
YS
Dooley
Alek N
AN
Huang
Jiang
J
Daridon
Antoine
A
Wyatt
Paul
P
Stout
David
D
Kolb
Hartmuth C
HC
Witte
Owen N
ON
Satyamurthy
Nagichettiar
N
Heath
James R
JR
Phelps
Michael E
ME
Quake
Stephen R
SR
Tseng
Hsian-Rong
HR
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
D015335:Molecular Probes; D019275:Radiopharmaceuticals; D012997:Solvents; D019788:Fluorodeoxyglucose F18; D005459:Fluorides