Harnessing the Maltodextrin Transport Mechanism for Targeted Bacterial Imaging: Structural Requirements for Improved in vivo Stability in Tracer Design

Axer, A; Hermann, S; Kehr, G; Clases, D; Karst, U; Fischer-Riepe, L; Roth, J; Fobker, M; Schäfers, M; Gilmour, R; Faust, A

Harnessing the Maltodextrin Transport Mechanism for Targeted Bacterial Imaging: Structural Requirements for Improved in vivo Stability in Tracer Design

Axer, A Hermann, S Kehr, G Clases, D

Karst, U Fischer-Riepe, L Roth, J Fobker, M Schäfers, M Gilmour, R Faust, A

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Publication Type:: Journal Article
Citation:: ChemMedChem, 2018, 13 (3), pp. 241 - 250
Issue Date:: 2018-02-06

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Field	Value	Language
dc.contributor.author	Axer, A	en_US
dc.contributor.author	Hermann, S	en_US
dc.contributor.author	Kehr, G	en_US
dc.contributor.author	Clases, D https://orcid.org/0000-0003-3880-9385	en_US
dc.contributor.author	Karst, U	en_US
dc.contributor.author	Fischer-Riepe, L	en_US
dc.contributor.author	Roth, J	en_US
dc.contributor.author	Fobker, M	en_US
dc.contributor.author	Schäfers, M	en_US
dc.contributor.author	Gilmour, R	en_US
dc.contributor.author	Faust, A	en_US
dc.date.issued	2018-02-06	en_US
dc.identifier.citation	ChemMedChem, 2018, 13 (3), pp. 241 - 250	en_US
dc.identifier.issn	1860-7179	en_US
dc.identifier.uri	http://hdl.handle.net/10453/130498
dc.description.abstract	© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Diagnosis and localization of bacterial infections remains a significant clinical challenge. Harnessing bacteria-specific metabolic pathways, such as the maltodextrin transport mechanism, may allow specific localization and imaging of small or hidden colonies. This requires that the intrabacterial tracer accumulation provided by the transporter is matched by high serum stability of the tracer molecule. Herein, radiolabeled maltodextrins of varying chain lengths and with free nonreducing/reducing ends are reported and their behavior against starch-degrading enzymes in the blood, which compromise their serum stability, is evaluated. Successful single-photon emission computed tomography (SPECT) imaging is shown in a footpad infection model in vivo by using the newly developed model tracer, [99mTc]MB1143, and the signal is compared with that of 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) as a nonbacterial specific marker for inflammation. Although the [99mTc]MB1143 imaging signal is highly specific, it is low, most probably due to insufficient serum stability of the tracer. A series of stability tests with different 18F-labeled maltodextrins finally yielded clear structural guidelines regarding substitution patterns and chain lengths of maltodextrin-based tracers for nuclear imaging of bacterial infections.	en_US
dc.relation.ispartof	ChemMedChem	en_US
dc.relation.isbasedon	10.1002/cmdc.201700543	en_US
dc.subject.classification	Medicinal & Biomolecular Chemistry	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Staphylococcus aureus	en_US
dc.subject.mesh	Staphylococcal Infections	en_US
dc.subject.mesh	Technetium	en_US
dc.subject.mesh	Fluorodeoxyglucose F18	en_US
dc.subject.mesh	Polysaccharides	en_US
dc.subject.mesh	Oligosaccharides	en_US
dc.subject.mesh	Contrast Media	en_US
dc.subject.mesh	Radiopharmaceuticals	en_US
dc.subject.mesh	Tomography, Emission-Computed, Single-Photon	en_US
dc.subject.mesh	Isotope Labeling	en_US
dc.subject.mesh	Molecular Structure	en_US
dc.subject.mesh	Oxidation-Reduction	en_US
dc.subject.mesh	Tissue Distribution	en_US
dc.title	Harnessing the Maltodextrin Transport Mechanism for Targeted Bacterial Imaging: Structural Requirements for Improved in vivo Stability in Tracer Design	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	13	en_US
utslib.for	0304 Medicinal and Biomolecular Chemistry	en_US
utslib.for	0305 Organic Chemistry	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
utslib.copyright.status	closed_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	13	en_US

Abstract:

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Diagnosis and localization of bacterial infections remains a significant clinical challenge. Harnessing bacteria-specific metabolic pathways, such as the maltodextrin transport mechanism, may allow specific localization and imaging of small or hidden colonies. This requires that the intrabacterial tracer accumulation provided by the transporter is matched by high serum stability of the tracer molecule. Herein, radiolabeled maltodextrins of varying chain lengths and with free nonreducing/reducing ends are reported and their behavior against starch-degrading enzymes in the blood, which compromise their serum stability, is evaluated. Successful single-photon emission computed tomography (SPECT) imaging is shown in a footpad infection model in vivo by using the newly developed model tracer, [99mTc]MB1143, and the signal is compared with that of 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) as a nonbacterial specific marker for inflammation. Although the [99mTc]MB1143 imaging signal is highly specific, it is low, most probably due to insufficient serum stability of the tracer. A series of stability tests with different 18F-labeled maltodextrins finally yielded clear structural guidelines regarding substitution patterns and chain lengths of maltodextrin-based tracers for nuclear imaging of bacterial infections.

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http://hdl.handle.net/10453/130498