In Vivo Visualization of Gastric, Colon, and Pancreatic Adenocarcinomas Using a Novel Cathepsin-Activated Fluorescent Probe VGT-309

INTRODUCTION: Growing interest exists in fluorescence-guided surgery (FGS) for accurate surgical staging in gastrointestinal adenocarcinomas. VGT-309 is a novel cathepsin-activated fluorescent probe visible in the near-infrared range. Cathepsin is upregulated in numerous solid cancers. The objective is to determine whether gastric, colon, and pancreatic adenocarcinomas can be visualized in mouse models with VGT-309. METHODS: Murine xenograft models were used in which pancreatic (AsPC-1-ffluc), gastric (MKN-74-ffluc), and colon (HT-29) cancer cell lines tagged with Luciferase were inoculated subcutaneously and intraperitoneally, N = 17. After adequate tumor growth, mice were intravenously injected with VGT-309 (2 mg/kg) and sacrificed 24 hours later. Near-infrared imaging was performed using a Pearl Imaging System and fluorescence signal was quantified. All results are reported as mean ± SD. RESULTS: VGT-309 fluorescence overlapped with that of Luciferase indicating successful VGT-309 imaging of tumor tissue. Tumor to muscle ratio of fluorescence for subcutaneously inoculated tumors was 6.03 ± 1.75 for AsPC-1-ffluc, 10.23 ± 2.23 for MKN-74-ffluc, and 11.92 ± 5.79 for HT-29. Similar results were noted for intraperitoneally inoculated tumors with ratios of 6.42 ± 3.11 for AsPC-1-ffluc, 13.473 ± 3.33 for MKN-74-ffluc, and 8.67 ± 2.62 for HT-29. Peritoneum demonstrated low fluorescence in both subcutaneous and intraperitoneal models. Liver, spleen, and kidney demonstrated fluorescence ratios similar to tumor in all cell lines (Figure).FigureCONCLUSION: VGT-309 is a cathepsin-based activatable fluorescent probe that can visualize gastric, colon, and pancreatic adenocarcinoma in vivo with a high signal-to-background ratio. Additional studies are warranted to support VGT-309 use in FGS for gastrointestinal adenocarcinomas.