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

Angew Chem Int Ed Engl. 2014 Jul 14;53(29):7669-73. doi: 10.1002/anie.201310979. Epub 2014 May 30.

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.

Keywords: FRET; fluorescence probes; homing; lipidation; tumor diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cathepsins / metabolism*
  • Lipid Metabolism*
  • Mice
  • Neoplasms, Experimental / enzymology
  • Neoplasms, Experimental / pathology*
  • Substrate Specificity

Substances

  • Cathepsins
  • cathepsin S