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Abstract #4534

Assessing host-tumour vasculature and glycolytic metabolism in response to hypoxia in a chick CAM model of GBM using MRI and MRS

Elisabeth Non Tudor Gash1,2, Sarah E Barnett3, Mahon Maguire2, Stephen Pickup4, Sonia Rocha5, Judy M Coulson1, and Harish Poptani1,2
1Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, United Kingdom, 2Centre for Preclinical Imaging, Liverpool Shared Research Facilities, University of Liverpool, Liverpool, United Kingdom, 3Egg Facility, Liverpool Shared Research Facilities, University of Liverpool, Liverpool, United Kingdom, 4Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States, 5Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, United Kingdom

Synopsis

Keywords: Biology, Models, Methods, Cancer, Glioblastoma, hypoxia, vasculature, metabolism, chick embryo CAM model

Motivation: Understanding vasculature, hypoxia and glycolysis in GBM is paramount towards understanding its resistance to therapies, but cannot be done in vitro. The CAM model is attractive as it provides the interaction between host vasculature and the tumour.

Goal(s): Optimise MRI and MRS to assess hypoxia, tumour-host vasculature and glycolytic metabolism in the GBM-CAM.

Approach: GBM-CAM xenografts were created under normoxic- and hypoxic-conditions. Imaging was performed using microscopy and MRI, and lactate detection via MRS.

Results: Distinct morphological differences in vasculature were identified between conditions. MRI revealed vessel penetration, MRS detected lactate levels, which were significantly higher in hypoxic tumours than in the CAM.

Impact: Developing tools to characterise vascular morphology and quantify lactate levels in the CAM GBM model can shed light on fundamental biological mechanisms, and support the development of therapeutic strategies for the clinic.

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Keywords