Surgical resection is often the first line of defense against cancers that are locally contained, where long-term control is the result of complete resection with margins negative for tumor tissue. Complete resection is a challenging task using the conventional surgical tools, which include white light illumination for visualization and palpation of the tumor bed. Fluorescence imaging has the potential to improve cancer detection, visualization and resection in the operating suite. To date a number of fluorescence image-guided surgery systems are either in clinical trial or approved for use in the clinic. However, the availability of clinically approved tissue- and/or disease-specific contrast agents to complement the fluorescence image-guided surgery systems is significantly lacking. A variety of fluorescence agents are under pre-clinical development where specificity for malignant tissue as well as signal to background ratio (SBR) are critical to the success of these novel agents. The strategy utilized herein to improve SBR in malignant tissues is termed “molecular beacons,” which consist of a fluorophore and a quencher in close proximity to one another linked by a peptide sequence. In the current work, the selected peptide sequence can be cleaved by metalloproteinases (MMPs), which are known to be overexpressed in various cancers. The molecular beacon demonstrated specificity for two preclinical oral carcinoma models when it was administered either via local injection intra- and peri-tumorally or applied topically at the surgical site, improving identification and visualization of the tumor tissue for resection. Utilization of fluorophores such as the molecular beacons demonstrated here could significantly improve tumor resection and facilitate accurate intraoperative margin assessment improving cancer therapy.

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