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beta-Configured clickable [F-18] FDGs as novel F-18-fluoroglycosylation tools for PET
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
Uppsala University, Sweden.
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
Uppsala University, Sweden.
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2017 (English)In: New Journal of Chemistry, ISSN 1144-0546, E-ISSN 1369-9261, Vol. 41, no 18, p. 10231-10236Article in journal (Refereed) Published
Abstract [en]

In oncology and neurology the F-18-radiolabeled glucose analogue 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) is by far the most commonly employed metabolic imaging agent for positron emission tomography (PET). Herein, we report a novel synthetic route to beta-configured mannopyranoside precursors and a chemoselective F-18-fluoroglycosylation method that employ two b-configured [F-18]FDG derivatives equipped with either a terminal azide or alkyne aglycon respectively, for use as a CuAAC clickable tool set for PET. The b-configured precursors provided the corresponding [F-18]FDGs in a radiochemical yield of 77-88%. Further, the clickability of these [F-18]FDGs was investigated by click coupling to the suitably functionalized Fmoc-protected amino acids, Fmoc-N-(propargyl)-glycine and Fmoc-3-azido-L-alanine, which provided the F-18-fluoroglycosylated amino acid conjugates in radiochemical yields of 75-83%. The F-18-fluoroglycosylated amino acids presented herein constitute a new and interesting class of metabolic PET radiotracers.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY , 2017. Vol. 41, no 18, p. 10231-10236
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:liu:diva-141934DOI: 10.1039/c7nj00716gISI: 000411767400073OAI: oai:DiVA.org:liu-141934DiVA, id: diva2:1149178
Note

Funding Agencies|Swedish Foundation for Strategic Research; Swedish Research Council

Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2018-02-21
In thesis
1. Synthesis and application of β-configured [18/19F]FDGs: Novel prosthetic CuAAC click chemistry fluoroglycosylation tools for amyloid PET imaging and cancer theranostics
Open this publication in new window or tab >>Synthesis and application of β-configured [18/19F]FDGs: Novel prosthetic CuAAC click chemistry fluoroglycosylation tools for amyloid PET imaging and cancer theranostics
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Positron emission tomography (PET) is a non-invasive imaging method that renders three-dimensional images of tissue that selectively has taken up a radiolabelled organic compound, referred to as a radiotracer. This excellent technique provides clinicians with a tool to monitor disease progression and to evaluate how the patient respond to treatment. The by far most widely employed radiotracer in PET is called 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), which is often referred to as the golden standard in PET. From a molecular perspective, [18F]FDG is an analogue of glucose where a hydroxyl group has been replaced with a radioactive fluorine atom (18F). It is well known that covalent attachment of carbohydrates (i.e., glycosylation) to biomolecules tend to improve their properties in the body, in terms of; improved pharmacokinetics, increased metabolic stability and faster clearance from blood and other non-specific tissue. It is therefore natural to pursuit the development of a [18F]fluoroglycosylation method where [18F]FDG is chemically conjugated to a ligand with high affinity for a given biological target (e.g., tumors or disease-associated protein aggregates).

This thesis describes a novel [18F]fluoroglycosylation method that in a simple and general manner facilitate the conjugation of [18F]FDG to biological ligands using click chemistry. The utility of the developed [18F]fluoroglycosylation method is demonstrated by radiolabelling of curcumin, thus forming a tracer that may be employed for diagnosis of Alzheimer’s disease. Moreover, a set of oligothiophenes were fluoroglycosylated for potential diagnosis of Alzheimer’s disease but also for other much rarer protein misfolding diseases (e.g., Creutzfeldt-Jakob disease and systemic amyloidosis). In addition, the synthesis of a series of 19F-fluoroglycosylated porphyrins is described which exhibited promising properties not only to detect but also to treat melanoma cancer. Lastly, the synthesis of a set of 19F-fluorinated E-stilbenes, structurally based on the antioxidant resveratrol is presented. The E-stilbenes were evaluated for their capacity to spectrally distinguish between native and protofibrillar transthyretin in the pursuit of finding diagnostic markers for the rare but severe disease, transthyretin amyloidosis.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. p. 100
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1900
Keywords
FDG, clickable, PET, synthesis, in vivo imaging, theranostics
National Category
Organic Chemistry
Identifiers
urn:nbn:se:liu:diva-144323 (URN)10.3384/diss.diva-144323 (DOI)9789176853764 (ISBN)
Public defence
2018-03-23, Planck, Fysikhuset, Campus Valla, Linköping, 09:15 (English)
Opponent
Supervisors
Available from: 2018-02-15 Created: 2018-01-15 Last updated: 2018-04-25Bibliographically approved

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