Journal
INVESTIGATIVE RADIOLOGY
Volume 40, Issue 6, Pages 321-327Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.rli.0000163797.23172.90
Keywords
optical imaging; breast cancer; proteases; cathepsin; molecular imaging
Funding
- NCI NIH HHS [R33 CA 91807] Funding Source: Medline
- NIBIB NIH HHS [R01 EB 000750-1] Funding Source: Medline
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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. Materials and Methods: Transgenic (FVB/N-TgN (WapHRAS)-69Lin y(SJL))) mice, which spontaneously develop breast cancer, were injected intravenously with a cathepsin-sensing fluorescent imaging probe. FRI and EMT 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 pen-nits 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.
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