Erika R. Amstalden1, Tiffany R. Greenwood2, Zaver M. Bhujwalla2, Venu Raman2, Ronald M. A. Heeren1, Kristine Glunde2
1FOM Institute for Atomic and Molecular Physics, Amsterdam, Netherlands; 2JHU ICMIC Program, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Breast tumors are characterized by spatially distinct hypoxic regions, which lead to radio- and chemoresistance and poor clinical outcome. Our goal is to identify to date unknown metabolites, small molecules, and proteins that, as a result of hypoxia-driven signaling pathways, have a high concentration in hypoxic regions. We combined 3D MRSI detection of metabolites with optical detection of hypoxic regions using hypoxia-driven fluorescence reporter and Imaging Mass Spectrometry (IMS) detection of undiscovered biomolecules in breast tumor models. Necrotic/hypoxic regions showed a markedly different molecular-metabolic profile compared to well-vascularized regions, which can provide molecular insights and differentiate these regions.