Imaging of differential protease expression in breast cancers for detection of aggressive tumor phenotypes

Radiology. 2002 Mar;222(3):814-8. doi: 10.1148/radiol.2223010812.


Purpose: To determine if different expression levels of tumor cathepsin-B activity in well differentiated and undifferentiated breast cancers could be revealed in vivo with optical imaging.

Materials and methods: A well differentiated human breast cancer (BT20, n = 8) and a highly invasive metastatic human breast cancer (DU4475, n = 8) were implanted orthotopically in athymic nude mice. Tumor-bearing animals were examined in vivo with near-infrared fluorescence (NIRF) imaging 24 hours after intravenous injection of an enzyme-sensing imaging probe. Immunohistochemistry, Western blotting (on cells and whole tumor samples), and correlative fluorescence microscopy were performed.

Results: Both types of breast cancers activated the NIRF probe so that tumors became readily detectable. However, in tumors of equal size, there was a 1.5-fold higher fluorescence signal in the highly invasive breast cancer (861 arbitrary units +/- 88) compared with the well differentiated lesion (566 arbitrary units +/- 36, P <.01). Western blotting confirmed a higher cathepsin-B protein content in the highly invasive breast cancer (DU4475) of about 1.4-fold (whole tumor samples) to 1.7-fold (cells). Immunohistochemistry and fluorescence microscopy findings confirmed the imaging findings.

Conclusion: Cathepsin-B enzyme activity can be determined in vivo with NIRF optical imaging, while differences in tumoral expression may correlate with tumor aggressiveness.

Publication types

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

MeSH terms

  • Adenocarcinoma / chemistry*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / secondary
  • Animals
  • Blotting, Western
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / pathology
  • Cathepsin B / analysis*
  • Female
  • Fluorescent Dyes
  • Humans
  • Immunohistochemistry
  • Mammary Neoplasms, Experimental / chemistry*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Spectroscopy, Near-Infrared*
  • Tumor Cells, Cultured


  • Fluorescent Dyes
  • Cathepsin B