1. Fluorescent Anti-MUC5AC Brightly Targets Pancreatic Cancer in a Patient-derived Orthotopic Xenograft
- Author
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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, and Bouvet, Michael
- Subjects
tumor-specific imaging ,Cancer Research ,Nude ,Clinical Sciences ,Mice, Nude ,digestive system ,General Biochemistry, Genetics and Molecular Biology ,fluorescence guided surgery ,PDOX ,Pancreatic Cancer ,Mice ,Rare Diseases ,fluids and secretions ,mucin ,antibody ,2.1 Biological and endogenous factors ,Animals ,Humans ,Oncology & Carcinogenesis ,Aetiology ,Cancer ,Fluorescent Dyes ,Pharmacology ,respiratory system ,MUC5AC ,Xenograft Model Antitumor Assays ,Pancreatic Neoplasms ,Orphan Drug ,Good Health and Well Being ,Heterografts ,sense organs ,Digestive Diseases ,Biotechnology ,Research Article - Abstract
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.
- Published
- 2021