Targeting MUC16 for fluorescence-guided surgery in pancreatic cancer

Pancreatic cancer is characterized by its poor prognosis. In the 2024, it is estimated that pancreatic cancer will be the cause of over 51,000 deaths. Surgical resection is currently the only curative treatment for pancreatic cancer, yet up to 90% of patients relapse after resection due to incomplete removal of the tumor. Fluorescence-guided surgery seeks to provide an intraoperative technique that allows surgeons to identify tumor margins during resection. We have developed an antibody-dye conjugate, NIRF-AR9.6, that targets mucin 16 (MUC16), which is expressed on pancreatic cancer, but not healthy pancreas or pancreatitis. In preclinical studies thus far, we have shown promising results in xenograft models of pancreatic cancer. We have now show recent results in orthotopically placed patient-derived xenografts (PDX) of pancreatic cancer to better recapitulate the tumor microenvironment. After 72 h post administration of NIRF-AR9.6, tumor-to-background ratios of 3 were achieved. Further optimization will be performed using PDX models of varying MUC16 levels, NIR fluorophore choice, and optimized timing.