Optical imaging of spontaneous breast tumors using protease sensing 'smart' optical probes.
OBJECTIVE
The objective of this study was to determine if spontaneous breast cancer lesions can be detected by fluorescence reflectance imaging (FRI) and fluorescence mediated tomography (FMT) using protease-sensing optical probes.


METHODS
Transgenic (FVB/N-TgN (WapHRAS)69Lin Y)) mice, which spontaneously develop breast cancer, were injected intravenously with a cathepsin-sensing fluorescent imaging probe. FRI and FMT were performed 24 hours after probe injection and region of interest (ROI) analysis was performed. Magnetic resonance images were acquired for anatomic coregistration with the FMT data. Moreover, correlative immunohistochemistry and fluorescence microscopy were performed.


RESULTS
All tumor nodules were clearly delineated by FRI showing an average signal intensity of 380 +/- 106 AU. Similarly, tumors were clearly detected by FMT imaging. Immunohistochemistry confirmed cathepsin-B expression of primary tumors and fluorescence microscopy revealed a strong Cy 5.5 deposition in the tissue.


CONCLUSIONS
FRI and FMT using "smart" protease sensing probes permits detection of experimental spontaneous breast cancers. Because the expression levels of various proteases correlate with patient outcome, this technique may not only help to detect, but also to differentiate breast cancers noninvasively.
Bremer
Christoph
C
Department of Clinical Radiology, University of Muenster, Germany. bremerc@uni-muenster.de
Ntziachristos
Vasilis
V
Weitkamp
Benedikt
B
Theilmeier
Gregor
G
Heindel
Walter
W
Weissleder
Ralph
R
D000818:Animals; D002403:Cathepsins / Q000032:analysis*; D003952:Diagnostic Imaging / Q000379:methods; D005456:Fluorescent Dyes; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D015335:Molecular Probes; D013050:Spectrometry, Fluorescence
D005456:Fluorescent Dyes; D015335:Molecular Probes; D002403:Cathepsins