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Review
. 2021 Nov 17;14(11):1175.
doi: 10.3390/ph14111175.

Sweetening Pharmaceutical Radiochemistry by 18F-Fluoroglycosylation: Recent Progress and Future Prospects

Sandip S Shinde  1 , Simone Maschauer  1 , Olaf Prante  1
Affiliations
Review

Sweetening Pharmaceutical Radiochemistry by 18F-Fluoroglycosylation: Recent Progress and Future Prospects

Sandip S Shinde et al. Pharmaceuticals (Basel). .

Abstract

In the field of 18F-chemistry for the development of radiopharmaceuticals for positron emission tomography (PET), various labeling strategies by the use of prosthetic groups have been implemented, including chemoselective 18F-labeling of biomolecules. Among those, chemoselective 18F-fluoroglycosylation methods focus on the sweetening of pharmaceutical radiochemistry by offering a highly valuable tool for the synthesis of 18F-glycoconjugates with suitable in vivo properties for PET imaging studies. A previous review covered the various 18F-fluoroglycosylation methods that were developed and applied as of 2014 (Maschauer and Prante, BioMed. Res. Int. 2014, 214748). This paper is an updated review, providing the recent progress in 18F-fluoroglycosylation reactions and the preclinical application of 18F-glycoconjugates, including small molecules, peptides, and high-molecular-weight proteins.

Keywords: 18F-fluoroglycosylation; PET; fluorine-18; positron emission tomography; prosthetic group.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Two-step 18F-fluoroglycosylation by click cycloaddition using 2-deoxy-2-[18F]fluoroglucopyranosyl azide (2), starting from the 2-O-triflate precursor of triacetylated β-mannosyl azide (1).
Figure 1
Figure 1
Click chemistry-based 2-deoxy-2-[18F]fluoroglycosylated ligands and their target receptors.
Scheme 2
Scheme 2
18F-fluoroglycosylation by CuAAC using 6-deoxy-6-[18F]fluoroglucopyranosyl azide 14 or 6´-deoxy-6´-[18F]fluoromaltosyl azide 17 with the cyclic peptide c(RGDfPra) alkyne (according to [26]).
Figure 2
Figure 2
Overview of PET tracers synthesized via CuAAC using the 18F-labeled prosthetic group 6-deoxy-6-[18F]fluoro-β-glucosyl azide (14). For a direct comparison (see text), the structures of 6′-deoxy-6′-[18F]fluoromaltosyl peptide 20 and 2-deoxy-2-[18F]fluoroglucosyl peptide 21 are included.
Figure 3
Figure 3
Overview of triazolylalkyl-linked 18F-glycoconjugates achieved by click chemistry-based 18F-fluoroglycosylation.
Figure 4
Figure 4
Examples of fluoroglycosylated compounds that have been studied for their biological activity prior to 18F-fluoroglycosylation.
Scheme 3
Scheme 3
18F-fluoroglycosylation via oxime formation using [18F]FDG.
Figure 5
Figure 5
18F-glycoconjugates synthesized by direct 18F-fluoroglycosylation through oxime formation with [18F]FDG.
Scheme 4
Scheme 4
18F-fluoroglycosylation via oxime formation using [18F]FDR.
Figure 6
Figure 6
18F-glycoconjugates synthesized by oxime formation with [18F]FDR.
See this image and copyright information in PMC

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