Exploiting the MUC5AC Antigen for Noninvasive Identification of Pancreatic Cancer.

Pancreatic cancer (PC) remains the 4th leading cause of cancer death; therefore, there is a clinically unmet need for novel therapeutics and diagnostic markers to treat this devastating disease. Physicians often rely on biopsy or CT for diagnosis, but more specific protein biomarkers are highly desired to assess the stage and severity of PC in a noninvasive manner. Serum biomarkers such as CA19.9 are of particular interest as they are commonly elevated in PC but have exhibited suboptimal performance in the clinic. MUC5AC has emerged as a useful serum biomarker that is specific for PC vs. inflammation. We developed RA96, an anti-MUC5AC antibody, to gauge its utility in PC diagnosis through immunohistochemical (IHC) analysis and whole-body PET in PC. Methods: In this study, extensive biochemical characterization determined MUC5AC as the antigen for RA96. We then determined the utility of RA96 for MUC5AC IHC on clinical PC and pre-clinical PC. Finally, we radiolabeled RA96 with zirconium-89 to assess its application as a whole-body PET radiotracer for MUC5AC quantification in PC. Results: Immunohistochemical staining with RA96 distinguished chronic pancreatitis (CP), PanIN, and varying grades of pancreatic ductal adenocarcinoma (PDAC) in clinical samples. [89Zr]Zr-DFO-RA96 was able to detect MUC5AC with high specificity in mice bearing capan-2 xenografts. Conclusion: Our study demonstrates that RA96 can differentiate between inflammation and PC, improving the fidelity of PC diagnosis. Our immuno-PET tracer [89Zr]Zr-DFO-RA96 shows specific detection of MUC5AC+ tumors in vivo, highlighting the utility of MUC5AC targeting for diagnosis of PC.