Localized Hypoxia Results in Spatially Heterogeneous Metabolic Signatures in Breast Tumor Models

Lu Jiang¹, Dmitri Artemov¹, Paul Winnard Jr.¹, Venu Raman¹, Zaver Bhujwalla¹, Kristine Glunde¹

Tumor hypoxia triggers signaling cascades that significantly impact on biological outcomes resulting in resistance to radio- and chemotherapy. Therefore, understanding the hypoxic response of tumors is critical. In this study, we have investigated the relationship between hypoxia, necrosis and several metabolites in a human breast cancer model by combining in vivo magnetic resonance imaging (MRI), magnetic resonance spectroscopic imaging (MRSI) with optical imaging of hypoxia and necrosis ex vivo. This multi-modal molecular imaging technology proved useful for delineating the effects of tumor hypoxia and necrosis on MRS-detectable metabolites, some of which may serve as markers for hypoxia and/or necrosis.