Precise tumor targeting and labeling with a fluorescent mucin 4 antibody for imaging patient-derived pancreatic cancer in a mouse model.

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 1mm(3) tumor fragments and implanted under the skin of the nude mouse. After the tumors grew similar to 5mm(3), two mice received 50 mu g and two mice received 75 mu g 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 mu g 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.