In Vivo Imaging of Tumors With Protease-Activated Near-Infrared Fluorescent Probes

Nat Biotechnol. 1999 Apr;17(4):375-8. doi: 10.1038/7933.

Abstract

We have developed a method to image tumor-associated lysosomal protease activity in a xenograft mouse model in vivo using autoquenched near-infrared fluorescence (NIRF) probes. NIRF probes were bound to a long circulating graft copolymer consisting of poly-L-lysine and methoxypolyethylene glycol succinate. Following intravenous injection, the NIRF probe carrier accumulated in solid tumors due to its long circulation time and leakage through tumor neovasculature. Intratumoral NIRF signal was generated by lysosomal proteases in tumor cells that cleave the macromolecule, thereby releasing previously quenched fluorochrome. In vivo imaging showed a 12-fold increase in NIRF signal, allowing the detection of tumors with submillimeter-sized diameters. This strategy can be used to detect such early stage tumors in vivo and to probe for specific enzyme activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Diagnostic Imaging
  • Endopeptidases / metabolism*
  • Female
  • Fluorescent Dyes* / metabolism
  • Humans
  • Infrared Rays*
  • Lysosomes / enzymology
  • Mice
  • Neoplasm Transplantation
  • Neoplasms, Experimental / diagnosis*
  • Neoplasms, Experimental / enzymology*
  • Neoplasms, Experimental / pathology
  • Tissue Distribution
  • Transplantation, Heterologous

Substances

  • Fluorescent Dyes
  • Endopeptidases