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In vivo imaging of mouse tumors by a lipidated cathepsin S substrate


Hu, Hai-Yu; Vats, Divya; Vizovisek, Matej; Kramer, Lovro; Germanier, Catherine; Wendt, K Ulrich; Rudin, Markus; Turk, Boris; Plettenburg, Oliver; Schultz, Carsten (2014). In vivo imaging of mouse tumors by a lipidated cathepsin S substrate. Angewandte Chemie Internationale Edition, 53(29):7669-7673.

Abstract

The synthesis and evaluation of two cathepsin S-specific probes is described. For long-term retention of the probe at the target site and a high signal-to-noise ratio, we introduced a lipidation approach via the simple attachment of palmitoic acid to the reporter. After cathepsin S-specific cleavage in cultured cells and in a grafted tumor mouse model, fluorescence increased owing to dequenching and we observed an intracellular accumulation of the fluorescence in the target tissue. The lipidated probe provided a prolonged and strongly fluorescent signal in tumors when compared to the very similar non-lipidated probe, demonstrating that non-invasive tumor identification is feasable. The homing principle by probe lipidation might also work for selective administration of cytotoxic compounds to specifically reduce tumor mass.

Abstract

The synthesis and evaluation of two cathepsin S-specific probes is described. For long-term retention of the probe at the target site and a high signal-to-noise ratio, we introduced a lipidation approach via the simple attachment of palmitoic acid to the reporter. After cathepsin S-specific cleavage in cultured cells and in a grafted tumor mouse model, fluorescence increased owing to dequenching and we observed an intracellular accumulation of the fluorescence in the target tissue. The lipidated probe provided a prolonged and strongly fluorescent signal in tumors when compared to the very similar non-lipidated probe, demonstrating that non-invasive tumor identification is feasable. The homing principle by probe lipidation might also work for selective administration of cytotoxic compounds to specifically reduce tumor mass.

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19 citations in Web of Science®
20 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Institute of Biomedical Engineering
Dewey Decimal Classification:570 Life sciences; biology
170 Ethics
610 Medicine & health
Language:English
Date:14 July 2014
Deposited On:03 Oct 2014 13:14
Last Modified:19 Feb 2017 08:33
Publisher:Wiley-VCH Verlag
ISSN:1433-7851
Publisher DOI:https://doi.org/10.1002/anie.201310979

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