Abstract 4301: Detection and characterization of regions of hypoxia within orthotopic pancreatic tumors using multispectral optoacoustic tomography

Abstract

Abstract Optical imaging is a vital tool in cancer research for visualization of tumors in preclinical models. However, resolution for bioluminescence and fluorescence modalities is restricted to a depth of five millimeters, as light is attenuated at increased depth and autofluorescence can create background noise. Light propagation becomes diffuse at only a few millimeters, resulting in light scattering and absorption. To improve imaging resolution and acquisition in real-time, multispectral optoacoustic tomography (MSOT) was utilized to visualize molecular phenomena such as the tissue oxygenation of characteristically hypoxic aggressive pancreatic tumors. SCID mice were orthotopically implanted with S2VP10L and MIA PaCa-2 pancreatic cancer cells that highly express the epidermal growth factor receptor (EGFR), which exhibits extracellular domain binding of the epidermal growth factor (EGF) ligand. Cohorts were then intravenously injected with fluorescent EGF ligand probes and imaged semiweekly to follow tumor growth and morphology. Medical Grade Air levels were set to 0.9 L and oxygen at 0.1 L to assess the correlation of increased hypoxia with tumor growth and progression. Pancreatic tumor cells were imaged concurrently with evaluating levels of oxygenated and deoxygenated hemoglobin, providing a distinct picture of the tumor and its vascularization. Use of MSOT to detect regions of hypoxia within tumor was validated using pimonidazole immunohistochemical staining of tumor tissue. For the first time, our data demonstrate regions of tumor hypoxia in living subjects, at depth, and noninvasively, via optoacoustic tomography. Dynamic assessment of tumor microenvironment, especially regions of tumor hypoxia, is essential to effectively target and treat tumors that are otherwise resistant to treatment. Citation Format: Shanice V. Hudson, Charles Kimbrough, Michael Egger, Anil Khanal, Michelle E. Smith, William E. Grizzle, Lacey R. McNally. Detection and characterization of regions of hypoxia within orthotopic pancreatic tumors using multispectral optoacoustic tomography. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4301. doi:10.1158/1538-7445.AM2014-4301