title: In vivo imaging of mouse tumors by a lipidated cathepsin S substrate.
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.
authors.affiliation: Cell Biology & Biophysics Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg (Germany); Sanofi Deutschland GmbH, Diabetes Division, R&D, Industriepark Park Höchst, 65926 Frankfurt (Germany).
authors.forename: Hai-Yu
authors.initials: HY
authors.lastname: Hu
authors.forename: Divya
authors.initials: D
authors.lastname: Vats
authors.forename: Matej
authors.initials: M
authors.lastname: Vizovisek
authors.forename: Lovro
authors.initials: L
authors.lastname: Kramer
authors.forename: Catherine
authors.initials: C
authors.lastname: Germanier
authors.forename: K Ulrich
authors.initials: KU
authors.lastname: Wendt
authors.forename: Markus
authors.initials: M
authors.lastname: Rudin
authors.forename: Boris
authors.initials: B
authors.lastname: Turk
authors.forename: Oliver
authors.initials: O
authors.lastname: Plettenburg
authors.forename: Carsten
authors.initials: C
authors.lastname: Schultz
mesh_terms: D000818:Animals; D002403:Cathepsins / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology*; D013379:Substrate Specificity
chemical_list: D002403:Cathepsins; C028217:cathepsin S
keywords: FRET; fluorescence probes; homing; lipidation; tumor diagnosis