Nucl Med Mol Imaging.  2009 Apr;43(2):91-99.

Nucleophilic Fluorination Reactions in Novel Reaction Media for 18F-Fluorine Labeling Method

• Kim DW
• Jeong HJ
• Lim ST
• Sohn MH

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 18F-fluorine. In this review we describe recent methods and novel trends for the introduction of 18F-fluorine into molecules which in turn are intended to serve as imaging agents for PET study. Nucleophilic 18F-fluorination of some halo- and mesyloxyalkanes to the corresponding 18F-fluoroalkanes with 18F-fluoride obtained from an 18O(p,n)18F reaction, using novel reaction media system such as an ionic liquidor tert-alcohol, has been studied as a new method for 18F-fluorine labeling. Ionic liquid method is rapid and particularly convenient because 18F-fluoride in H2O 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 18F-fluorine for PETimaging, and it is illustrated by the synthesis of 18F-fluoride radiolabeled molecular imaging probes, such as 18F-FDG, 18F-FLT, 18F-FP-CIT, and 18F-FMISO, in high yield and purity and in shorter times compared to conventional syntheses

Keyword

Nucleophilic fluorination; 18F-fluorine; ionic liquid; tert-alcohol; PET

MeSH Terms

Biological Processes
Dideoxynucleosides
Fluorides
Fluorodeoxyglucose F18
Halogenation
Humans
Imidazoles
Misonidazole
Molecular Imaging
Nitro Compounds
Organothiophosphorus Compounds
Positron-Emission Tomography
Radiopharmaceuticals
Solvents
Dideoxynucleosides
Fluorides
Fluorodeoxyglucose F18
Imidazoles
Misonidazole
Nitro Compounds
Organothiophosphorus Compounds
Radiopharmaceuticals
Solvents