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.Pancreatic cancer is the fourth-leading cause of cancer death in the United States (1, 2). Over 60,000 people are estimated to be diagnosed with pancreatic cancer and >48,000 will die from it in the United States in 2021 (2). Of people diagnosed with pancreatic cancer, 90% of them will die from the disease (1).The only current curative treatment for pancreatic cancer is surgical resection (1). However, most patients are diagnosed with advanced disease, with only 15-20% considered surgical candidates (3). Of those that undergo surgical resection, 50-80% have positive microscopic resection margins (R1), a poor-prognosis indicator. Over 60% of patients will develop recurrence of disease within 2 years of their operation (4, 5). Therefore, improved methods of pancreatic cancer therapeutics are needed.Mucins, glycoproteins involved in cell signaling and barrier protection, are overexpressed in pancreatic cancer (6, 7); specifically, mucin-5AC (MUC5AC), which has minimal or no expression in healthy pancreatic tissue (8-10). Jonckheere et al. performed mucin staining in normal pancreatic tissue, pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC). MUC5AC expression was found in 2-4% of normal ducts but its overexpression was found in 70% of PanIN IA cases and 85% of PDAC (9). In the present study, fluorescent-tagged antibodies to MUC5AC were tested with tumor lysates of pancreatic cancer and pancreaticcancer patient-derived orthotopic xenograft (PDOX) models. Materials and MethodsMice. Athymic nude mice, aged 4-6 weeks, were purchased from The Jackson Laboratory (Bay Harbor, ME, USA). The mice were housed in a barrier facility and fed an autoclaved laboratoryapproved diet. The mice were anesthetized with intraperitoneal injection of a solution of xylazine, ketamine and phosphate-buffered saline (PBS) prior to all surgical procedures. At the conclusion of the study, mice were euthanized with CO 2 inhalation or cervica...

Colorectal cancer (CRC) is a common cause of cancer and cancer-related death. Surgery is the only curative modality. Fluorescence-enhanced visualization of CRC with targeted fluorescent probes that can delineate boundaries and target tumor-specific biomarkers can increase rates of curative resection. Approaches to enhancing visualization of the tumor-to-normal tissue interface are active areas of investigation. Nonspecific dyes are the most-used approach, but tumor-specific targeting agents are progressing in clinical trials. The present narrative review describes the principles of fluorescence targeting of CRC for diagnosis and fluorescence-guided surgery with molecular biomarkers for preclinical or clinical evaluation.

HopQ is an outer-membrane protein of Helicobacter pylori that binds to human carcinoembryonic antigen-related cell-adhesion molecules (CEACAMs) with high specificity. We aimed to investigate fluorescence targeting of CEACAM-expressing colorectal tumors in patient-derived orthotopic xenograft (PDOX) models with fluorescently labeled recombinant HopQ (rHopQ). Western blotting, flow cytometry and ELISA were performed to determine the efficiency of rHopQ binding to CEACAMs. rHopQ was conjugated to IR800DyeCW (rHopQ-IR800). Nude mice received orthotopic implantation of colon cancer tumors. Three weeks later, mice were administered 25 μg or 50 μg HopQ-IR800 and imaged 24 or 48 h later. Intravital images were analyzed for tumor-to-background ratio (TBR). Flow cytometry and ELISA demonstrated binding of HopQ to CEACAM1, 3 and 5. Dose-response intravital imaging in PDOX models demonstrated optimal results 48 h after administration of 50 μg rHopQ-IR800 (TBR = 3.576) in our protocol. Orthotopic models demonstrated clear tumor margins of primary tumors and small regional metastases with a mean TBR = 3.678 (SD ± 1.027). rHopQ showed specific binding to various CEACAMs in PDOX models. rHopQ may be useful for CEACAM-positive tumor and metastasis detection for pre-surgical diagnosis, intra-operative imaging and fluorescence-guided surgery.