In Vivo Imaging of Mouse Tumors by a Lipidated Cathepsin S Substrate |
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Authors: | Lovro Kramer Catherine Germanier Dr. K. Ulrich Wendt Prof. Markus Rudin Prof. Boris Turk Dr. Oliver Plettenburg Priv.‐Doz. Dr. Carsten Schultz |
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Affiliation: | 1. Jozef Stefan Institute, Department of Biochemistry and Molecular Biology, Jamova 39, 1000 Ljubljana (Slovenia);2. International Postgraduate School Jozef Stefan, Ljubljana (Slovenia);3. Institute for Biomedical Engineering, ETH Zürich and University of Zürich (Switzerland);4. Sanofi Deutschland GmbH, Diabetes Division, R&D, Industriepark Park H?chst, 65926 Frankfurt (Germany);5. Center of Excellence CIPKEBIP, Ljubljana (Slovenia);6. Faculty of Chemistry and Chemical Technology, University of Ljubljana (Slovenia);7. Cell Biology & Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg (Germany) |
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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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Keywords: | fluorescence probes FRET homing lipidation tumor diagnosis |
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