Cathepsin-sensing optical probe detects breast cancer lesions in mouse study

November 4, 2005



CONTEXT: Proteases play a key role in cancer progression because of their involvement in the degradation of the extracellular matrix and basement membranes. In breast cancer, increased expression of cathepsin-B and other thiol proteases has been associated with increased aggressiveness and poor outcomes. Protease-sensing optical probes have been used in a variety of oncologic imaging applications. Dr. Christoph Bremer and colleagues at Massachusetts General Hospital and the University of Muenster in Germany examined the ability of a cathepsin-sensing fluorescent imaging probe to detect spontaneous breast cancer lesions.

RESULTS: Transgenic mice that spontaneously develop breast cancer were injected with a cathepsin-sensing imaging probe. Fluorescence reflectance imaging (FRI) and fluorescence-mediated tomography (FMT) were performed 24 hours after injection. MR images were obtained for anatomic coregistration with FMT. Both FRI and FMT imaging clearly delineated tumor nodules. Immunohistochemistry confirmed cathepsin-B expression by primary tumors.

IMAGE: FMT images were acquired at different levels in the tumor region, as illustrated in the corresponding sagittal MR images (left). After injection of the optical probe, strong tissue fluorescence could be reconstructed in the tumor region (right).

IMPLICATIONS: Because the expression of various proteases correlates with patient outcome, FRI and FMT with protease-sensing optical probes may offer a means of breast cancer detection. The imaging techniques may also be useful in noninvasive differentiation of breast tumors and may have application in the monitoring of treatment with protease inhibitors.