Near-infrared fluorescent imaging of pancreatic cancer in mice using a novel antibody to CEACAM5

The silent nature of pancreatic cancer disease progression emphasizes the need for early detection as a strategy for improving patient outcome. CEACAM5 is a well-known tumor marker overexpressed in many human cancers, including the pancreas. In this study we utilized a novel monoclonal antibody against CEACAM5, the C1P83 antibody. This antibody reacts to the Gold epitope 3 of CEACAM5. We tested the C1P83 antibody in a mouse model of orthotopic pancreatic tumor to determine diagnostic potential as a single agent. Four-week-old female immunodeficient C57BL/6 FoxN1nu mice (Harlan) were used for establishing subcutaneous tumor model with C15A3 cells or orthotopical tumor model with the human pancreatic cell line BXPC3. Conjugation of C1P83, and mouse IgG was performed using IRD800CW near-infrared fluorescent dye (LiCOR). Tumor growth were monitored by ultrasound or MRI and tumors were allowed to grow for 10-14 days before imaging. Purified conjugates of C1P83-IRDye800CW were tested for binding selectivity in vitro of human BxPC-3 cancer cells that express CEACAM5, and the Binding was time-dependent. Conjugates failed to label the PANC-1 cells which is a CEACAM5 negative control. In the subcutaneous tumor model in immunodeficient mice, subcutaneously inoculated tumors of C15A3 cells, which express CEACAM5, were visualized with high sensitivity. In the orthotopic pancreatic model, C1P83-conjugates can be applied for visualization of the CEACAM5 positive orthotopic pancreatic tumor. Results of ex vivo were comparable to those obtained in vivo. Overall, fluorescent conjugates of C1P83-IRDye800CW were sensitive for detection of pancreatic cancer by targeting CEACAM5. In conclusion, fluorescent C1P83-IRDye800CW conjugates were sensitive and selective for NIR fluorescent detection of pancreatic cancer by targeting CEACAM5. The CEACAM5 epitope GOLD 3 is a potential molecular target for NIR fluorescent molecular imaging. This NIR fluorescent imaging modality based on the monoclonal antibody of C1P83 is expected to evolve into future fluorescent surgical navigation.


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