Abstract 4103: Utility of multispectral optoacoustic tomography in imaging pancreatic tumors using a uPA-probe

Abstract

Abstract Background: Pancreatic cancer has the lowest 5-year survival rate of all cancer types. Current methods of pancreatic cancer screening, diagnosis and treatment have failed to improve outcome in the last few decades. Potential explanation for this failure may be explained by the hypovascularized nature of pancreatic cancer, making conventional chemotherapy and imaging modality suboptimal. There is a potential for improved imaging using a new imaging modality, multispectral optoacoustic tomography (MSOT). We hypothesize that a using urokinase plasminogen activator (uPA) contrast agent while using MSOT imaging would improve identification of orthotopic pancreatic cancer in xenografts. Methods: Expression of uPA receptor (uPAR) were evaluated in pancreatic tumor cell lines, Panc1, S2CP9, MiaPaca-2 and S2VP10 using western blot. A uPA targeted contrast agent was created using standard bioconjugation methods with the Hilite 750 near infrared (NIR) dye. Five SCID mice were orthotopically implanted with S2CP9 (1.5 x 105) and 5 additional SCID mice were implanted with MiaPaCa2 (2.0 x 106) pancreatic tumor cells. When tumor size reached 3mm, 200µL of 100 nM uPA-750 probe or 750 dye alone was injected into mice. Biodistribution and accumulation of the uPA-750 probe was visualized using MSOT imaged at 2-hour intervals for 8 hours and at 24 hours. Accumulation of uPA-750 probe was evaluated in the tumor, liver, and kidney using NIR fluorescent imaging. Results: All pancreatic cancer cell line expressed uPAR with the highest in S2CP9 cells (3.0x), S2VP10 (2.5x), Panc1 (1.77x) and MiaPaca-2 (1.3x). In vivo, peak intensity of uPA-750 probe was successfully detected using MSOT at 4 hours, within the pancreas tumor in slices from 37mm-41mm. uPA-750 probe was undetectable within the tumor after 8 hours. Using ex vivo NIR fluorescence imaging, uPA-probe signal was detected only within the pancreatic tumor, however, no signal was detected in the liver or kidney. Conclusion: This study demonstrated MSOT imaging using uPA-probe as a contract agent may lead to improved pancreatic cancer detection which may lead to improvement in overall outcome. Citation Format: Akiko Chiba, Abhilash Samykutty, Mary Smith, Lacey McNally. Utility of multispectral optoacoustic tomography in imaging pancreatic tumors using a uPA-probe [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4103.