Abstract PO-038: DCE-MRI of tumor hypoxia in cervical carcinoma and pancreatic ductal adenocarcinoma xenografts

Abstract

Tumor hypoxia is associated with resistance to treatment, aggressive growth, and poor clinical outcome in many cancer types, and is a result of an imbalance between oxygen supply and oxygen consumption. We have previously shown that Ktrans and ve images derived by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) reflect blood perfusion and cell density which are important determinants of oxygen supply and oxygen consumption respectively. The purpose of the current study was to investigate whether Ktrans and/or ve images can be used to produce images of tumor hypoxia. Cervical carcinoma and pancreatic ductal adenocarcinoma xenografts were used as models of human cancer, and xenografted tumors were subjected to antiangiogenic treatment or left untreated. Ktrans and ve images were derived from DCE-MRI data by using Tofts standard pharmacokinetic model, and images of tumor hypoxia were produced by applying threshold values to Ktrans and/or ve. Tumor hypoxia was also assessed by immunohistochemistry by using pimonidazole as a hypoxia marker. Ktrans and ve images were highly heterogeneous. Strong correlations were found between hypoxic fractions determined by immunohistochemistry and hypoxic fractions calculated by using Ktrans but not ve images. Importantly, hypoxia images produced by using Ktrans images reflected both naturally occurring and treatment-induced hypoxia. Moreover, hypoxia images produced by combining Ktrans and ve images were not superior to the hypoxia images produced by using only Ktrans images. These observations imply that Ktrans images reflected blood perfusion and oxygen supply, and that the heterogeneity in hypoxia was caused by heterogeneity in oxygen supply rather than heterogeneity in cell density and oxygen consumption in these tumor models. Citation Format: Jon-Vidar Gaustad, Anette Hauge, Catherine S. Wegner, Lise Mari K. Hansem, Einar K. Rofstad. DCE-MRI of tumor hypoxia in cervical carcinoma and pancreatic ductal adenocarcinoma xenografts [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-038.