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Nucleophilic Fluorination Reactions in Novel Reaction Media for $^{18}F$-Fluorine Labeling Method  

Kim, Dong-Wook (Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital)
Jeong, Hwan-Jeong (Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital)
Lim, Seok-Tae (Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital)
Sohn, Myung-Hee (Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital)
Publication Information
Nuclear Medicine and Molecular Imaging / v.43, no.2, 2009 , pp. 91-99 More about this Journal
Abstract
Noninvasive imaging of molecular and biological processes in living subjects with positron emission tomography(PET) provides exciting opportunities to monitor metabolism and detect diseases in humans. Measuring these processes with PET requires the preparation of specific molecular imaging probes labeled with $^{18}F$-fluorine. In this review we describe recent methods and novel trends for the introduction of $^{18}F$-fluorine into molecules which in turn are intended to serve as imaging agents for PET study. Nucleophilic $^{18}F$-fluorination of some halo- and mesyloxyalkanes to the corresponding $^{18}F$-fluoroalkanes with $^{18}F$-fluoride obtained from an $^{18}O(p,n)^{18}F$ reaction, using novel reaction media system such as an ionic liquidor tert-alcohol, has been studied as a new method for $^{18}F$-fluorine labeling. Ionic liquid method is rapid and particularly convenient because $^{18}F$-fluoride in $H_2O$ can be added directly to the reaction media, obviating the careful drying that is typically required for currently used radiofluorination methods. The nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with $^{18}F$-fluorine for PETimaging, and it is illustrated by the synthesis of $^{18}F$-fluoride radiolabeled molecular imaging probes, such as $^{18}F$-FDG, $^{18}F$-FLT, $^{18}F$-FP-CIT, and $^{18}F$-FMISO, in high yield and purity and in shorter times compared to conventional syntheses.
Keywords
Nucleophilic fluorination; $^{18}F$-fluorine; ionic liquid; tert-alcohol; PET;
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