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Fluorescent Anti-MUC5AC Brightly Targets Pancreatic Cancer in a Patient-derived Orthotopic Xenograft
- Turner, Michael A;
- Hollandsworth, Hannah M;
- Nishino, Hiroto;
- Amirfakhri, Siamak;
- Lwin, Thinzar M;
- Lowy, Andrew M;
- Kaur, Sukhwinder;
- Natarajan, Gopalakrishnan;
- Mallya, Kavita;
- Hoffman, Robert M;
- Batra, Surinder K;
- Bouvet, Michael
Published Web Location
https://doi.org/10.21873/invivo.12676Abstract
BACKGROUND: Overexpression of mucin-5AC (MUC5AC) makes it a targetable biomarker in pancreatic cancer. The present study evaluated tumor targeting with a MUC5AC antibody conjugated to a near-infrared dye in a patient-derived orthotopic xenograft (PDOX) mouse model. MATERIALS AND METHODS: MUC5AC monoclonal antibody was conjugated to the near-infrared dye IRDye800CW to synthesize MUC5AC-IR800. PDOX models were established by implanting a high-MUC5AC-expressing patient-derived pancreatic tumor on the pancreas of nude mice. After 4 weeks of PDOX tumor growth, mice were imaged after receiving MUC5AC-IR800 (75 μg) intravenously. RESULTS: In the PDOX models, MUC5AC-IR800 selectively and brightly targeted the pancreatic tumor (tumor to background ratio: 2.46±0.465). CONCLUSION: MUC5AC-IR800 provides distinct visualization of pancreatic tumors. MUC5AC-IR800 may be used clinically in the future to improve pancreatic cancer resection. This novel fluorescent probe is also promising for targeting of pre-malignant pancreatic lesions with subsequent resection under fluorescence guidance.
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