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Imaging of Differential Protease Expression in Breast Cancers for Detection of Aggressive Tumor Phenotypes¹

¹ From the Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Boston. Received April 19, 2001; revision requested May 25; revision received June 22; accepted July 16. Supported in part by NIH NOI-C0M065, P50-CA86355-01, and a Dana Farber grant. C.B. supported by the Deutsche Forschungsgemeinschaft. Address correspondence to C.B., Department of Clinical Radiology, University of Muenster, Albert-Schweitzer-Strasse 33, D-48129 Muenster, Germany (e-mail: bremerc@umi-muenster.de).

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.

© RSNA, 2002

Index terms: Breast neoplasms, experimental studies • Infrared and near-infrared spectroscopy • Animals

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