Selective tumor targeting with a fluorescent MUC4 antibody in a patient derived pancreatic cancer xenograft mouse model

Abstract

Introduction The 5 year survival rate of pancreatic cancer is <10%. Most patients have metastatic disease at time of diagnosis, often to the liver. Innovative imaging modalities, i.e. fluorescence guided surgery (FGS), may better appreciate metastatic disease and guide treatment. Mucin 4 (MUC4), a glycoprotein, is found in 89% of pancreatic cancers and absent in normal pancreatic tissue making it a candidate for tumor targeting in FGS. In the present study, a fluorescently-labeled MUC4 antibody preferentially targets patient pancreatic cancer in a mouse model. Methods and Materials A MUC4 antibody was conjugated to the infrared dye IRDye800CW (LICOR, Lincoln, NE) to synthesize MUC4-IR800. A high MUC4 expressing patient-derived hepatic metastatic pancreatic tumor (Panc Met) was divided into 1mm3 tumor fragments and implanted under the skin of the nude mouse. After the tumors grew ~5mm3, two mice received 50 μg and two mice received 75 μg of MUC4-IR800 via tail vein injection. Daily in-vivo imaging was performed with the Pearl Trilogy Imager (LICOR, Lincoln, NE) for 3 days. Tumor to background ratios (TBR) were calculated using skin as background. Results MUC4-IR800 selectively imaged the Panc Met tumors (see figure below). TBRs for all time points and doses were <2. The 75 μg arm had higher TBRs at 24 and 72 hours. At 48 hours, the TBRs were the same. Conclusion This present study demonstrated the successful targeting of a patient hepatic metastatic pancreatic cancer mouse model with MUC4-IR800. This has potential to improve metastatic pancreatic cancer detection. Future studies will be conducted with orthotopic models.