Abstract 4161: Identification of pancreatic adenocarcinoma using urokinase plasminogen activator probe detected using optoacoustic imaging

Abstract

Abstract Purpose: Diagnosing and treating pancreatic cancer remains a challenge. The hypovascularized nature of pancreatic cancer renders modern chemotherapeutics and cancer detection contrast agents ineffective. A promising approach to the challenges is the adoption of a novel imaging technique known as Multispectral Tomography (MSOT). We hypothesize that a urokinase plasminogen activator (UPA) probe will enhance the detection of orthotopic pancreatic cancer xenografts. Methods: Pancreatic tumor cell lines (Panc1, MiaPaca-2, S2VP10, and S2C9) were assessed for UPA-receptor expression using western blot analysis. UPA peptide was synthesized and to the HiLyte-750 NIR dye. Flow cytometry and immunofluorescence were utilized to examine the specificity and activity of this UPA-750. The UPA-750 binding efficiency was assessed through a competitive inhibition assay with a UPAR-blocking antibody using fluorescence microscopy. Then SCID mice (5 mice/group) received orthotopic implantation of S2C9 (1.5 x 105) or MiaPaCa2 (2.0 × 106) pancreatic tumor cells. UPA-750 or 750 dye alone was IV injected into mice after the tumors reached 3mm. Biodistribution and accumulation of UPA-750 were observed through MSOT images taken at 2-hour intervals over 8 hours and at 24 hours. UPA-750 in the tumor, liver, and kidney was confirmed through ex vivo fluorescent imaging. Results: UPAR expression was observed in every pancreatic cancer cell line, with the greatest relative abundance in S2P9 cells (3.0X), followed by S2VP10 (2.5X), Panc1 (1.77X), and MiaPaca-2 (1.3X). Application of the UPAR blocking antibody on S2CP9, S2VP10, MiaPaCa2, and SKOV3p1 (positive control) cell lines resulted in the inhibition of cellular binding of the UPA-750, as evidenced by fluorescence microscopy. UPA-probe was successfully observed in pancreas tumor slices with peak intensity at 4-hrs of imaging by MSOT. Ex vivo NIR fluorescence imaging confirmed UPA-750 signal in pancreatic tumors but not in liver or kidney. Conclusion: UPA-probe exhibits potential as a marker for pancreatic cancer. Citation Format: Vung Kim, Phillip Chuong, Ryan Bynum, William Grizzle, Lacey R. McNally. Identification of pancreatic adenocarcinoma using urokinase plasminogen activator probe detected using optoacoustic imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4161.