Pancreatic cancer is the third leading cause of cancer-related deaths in the United States. Up to 20% of patients are candidates for resection, which is currently the only potentially curative treatment option. However, pancreatic cancer patients have high rates of recurrence after resection due in part to cells left behind at the surgical margin. Fluorescence guided surgery (FGS) has emerged as a method to improve surgical resection. For pancreatic cancer patients eligible for surgical resection, intraoperative imaging would serve two purposes. For patients with resectable disease, image-guidance could help delineate tumor tissue to achieve complete resection. Of critical value, fluorescence guided surgery (FGS) could be used to identify locally metastatic disease, which could spare the patient from major, unnecessary surgery and move directly to other treatments. Recent studies demonstrated that MUC16 is overexpressed in 60-80% of pancreatic cancers, but this biomarker has not yet been explored for FGS of pancreatic cancer. Herein, we describe the validation and development of a near infrared fluorescence antibody that recognizes MUC16 for surgical imaging.
Breast cancer patients that experience complete removal of the primary tumor, or negative surgical margins (NSMs), benefit from decreased rates of local recurrence and increased survival. However, intraoperative margin detection is limited to visualization, palpation, and experience to identify malignant vs. healthy tissue. As a result, roughly 1/3 of patients treated with breast conserving surgery (BCS) have residual cancer cells left at the resection border, or positive surgical margins (PSMs). Fluorescence image-guided surgery (FIGS) is a promising alternative for intraoperative margin detection, providing surgeons with real-time feedback on tumor location, increasing the likelihood of achieving NSMs. Our past work has demonstrated that the use of self-assembled hyaluronic acid (HA) nanoparticles improves the delivery of indocyanine green (ICG) to breast tumors, enhancing intraoperative tumor signal and contrast. This study built upon these findings by assessing the surgical efficacy of ICG-loaded HA nanoparticles (NanoICG) for the image-guided resection of orthotopic iRFP+/luciferase+ 4T1 breast tumors in BALB/c mice. Tumors were resected with FIGS in mice treated with ICG or NanoICG and compared to bright light surgery (BLS) or sham controls. Tumor growth and recurrence were monitored with bioluminescence imaging. NanoICG improved complete resection and prolonged tumorfree survival. Additionally, NanoICG provided greater intraoperative contrast in malignant tissue than ICG or BLS. Furthermore, NanoICG demonstrated a greater ability to identify small, occult lesions than ICG. Overall, the use of NanoICG for the fluorescence image-guided resection of breast tumors could potentially decrease PSM rates and improve complete tumor removal.
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