Abstract
Fluorine-18 (18F, β+; 96.7%, T1/2=109.8 min) is of considerable importance for developing positron emission tomography (PET) ligands for imaging receptor, enzyme, gene expression etc. in brain, tumor, myocardium and other regions or organs due to its optimal decay characteristics. To synthesize 18F-labeled PET ligands, reliable labeling techniques inserting 18F into a target molecule are necessary. [18F]Fluoroalkylation is a useful way of introducing 18F into target molecules containing amino, phenol, thiophenol, and amide functional groups. Here, we review the preparation, reactivity and application of [18F]fluoroalkyl agents for the development of 18Flabeled PET ligands in molecular imaging. [18F]Fluoroalkyl agents have been synthesized by reacting [18F]F- with the corresponding alkyl derivatives containing halogen and sulfonate as leaving groups. After the fluorination reaction, the radiolabeled products with relatively low boiling points were distilled from the reaction mixtures, sometimes added by Sep-Pak or gas chromatography separation. The [18F]fluoromethyl agents have high reactivity with nucleophilic substrates, but many [18F]fluoromethylated compounds are in vitro unstable. To increase the efficiency of [18F]fluoroethylation, [18F]FCH2CH2Br, the most frequently used [18F]fluoroethyl agent, was converted into [18F]FCH2CH2I or [18F]FCH2CH2OTf in situ. Most [18F]fluoromethylated ligands were found to be in vivo unstable due to defluorination. Deuterium substitution for the fluoromethyl group reduced defluorination to an extent. A number of [18F]fluoroethylated PET ligands have been developed for animal evaluation and clinical investigation.
Keywords: Fluorine-18, [18F]Fluoromethylation, [18F]Fluoroethylation, PET, Molecular imaging
Current Topics in Medicinal Chemistry
Title: [18F]Fluoroalkyl Agents: Synthesis, Reactivity and Application for Development of PET Ligands in Molecular Imaging
Volume: 7 Issue: 18
Author(s): Ming-Rong Zhang and Kazutoshi Suzuki
Affiliation:
Keywords: Fluorine-18, [18F]Fluoromethylation, [18F]Fluoroethylation, PET, Molecular imaging
Abstract: Fluorine-18 (18F, β+; 96.7%, T1/2=109.8 min) is of considerable importance for developing positron emission tomography (PET) ligands for imaging receptor, enzyme, gene expression etc. in brain, tumor, myocardium and other regions or organs due to its optimal decay characteristics. To synthesize 18F-labeled PET ligands, reliable labeling techniques inserting 18F into a target molecule are necessary. [18F]Fluoroalkylation is a useful way of introducing 18F into target molecules containing amino, phenol, thiophenol, and amide functional groups. Here, we review the preparation, reactivity and application of [18F]fluoroalkyl agents for the development of 18Flabeled PET ligands in molecular imaging. [18F]Fluoroalkyl agents have been synthesized by reacting [18F]F- with the corresponding alkyl derivatives containing halogen and sulfonate as leaving groups. After the fluorination reaction, the radiolabeled products with relatively low boiling points were distilled from the reaction mixtures, sometimes added by Sep-Pak or gas chromatography separation. The [18F]fluoromethyl agents have high reactivity with nucleophilic substrates, but many [18F]fluoromethylated compounds are in vitro unstable. To increase the efficiency of [18F]fluoroethylation, [18F]FCH2CH2Br, the most frequently used [18F]fluoroethyl agent, was converted into [18F]FCH2CH2I or [18F]FCH2CH2OTf in situ. Most [18F]fluoromethylated ligands were found to be in vivo unstable due to defluorination. Deuterium substitution for the fluoromethyl group reduced defluorination to an extent. A number of [18F]fluoroethylated PET ligands have been developed for animal evaluation and clinical investigation.
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Zhang Ming-Rong and Suzuki Kazutoshi, [18F]Fluoroalkyl Agents: Synthesis, Reactivity and Application for Development of PET Ligands in Molecular Imaging, Current Topics in Medicinal Chemistry 2007; 7 (18) . https://dx.doi.org/10.2174/156802607782507448
DOI https://dx.doi.org/10.2174/156802607782507448 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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