Combined endogenous MR biomarkers to predict basal tumor oxygenation and response to hyperoxic challenge. (11th October 2017)

• Record Type: Journal Article
• Authors: Cao‐Pham, Thanh‐Trang; Joudiou, Nicolas; Van Hul, Matthias; Bouzin, Caroline; Cani, Patrice D.; Gallez, Bernard; Jordan, Bénédicte F.
• Is Part Of: NMR in biomedicine. Volume 30:Number 12(2017:Dec.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-10-11
• Subjects: ΔR1 -- ΔR2* -- carbogen -- MRI -- tumor hypoxia; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.3836
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : Hypoxia is a common feature of solid tumors, which translates into increased angiogenesis, malignant phenotype cell selection, change in gene expression and greater resistance to radiotherapy and chemotherapy. Therefore, there is a need for markers of hypoxia to stratify patients, in order to personalize treatment to improve therapeutic outcome. However, no modality has yet been validated for the screening of hypoxia in routine clinical practice. Magnetic resonance imaging (MRI) R 1 and R 2 * relaxation parameters are sensitive to tissue oxygenation: R 1 is sensitive to dissolved oxygen and R 2 * is sensitive to intravascular deoxyhemoglobin content. Two rat tumor models with distinct levels of hypoxia, 9L–glioma and rhabdomyosarcoma, were imaged for R 1 and R 2 * under air and carbogen (95% O2 and 5% CO2 ) breathing conditions. It was observed that the basal tumor oxygenation level had an impact on the amplitude of response to carbogen in the vascular compartment ( R 2 *), but not in the tissue compartment ( R 1 ). In addition, the change in tissue oxygenation estimated by Δ R 1 correlated with the change in vascular oxygenation estimated by Δ R 2 *, which is consistent with an increase in oxygen supply generating an elevated tumor p O2 . At the intra‐tumoral level, we identified four types of voxel to which a hypoxic feature was attributed (mild hypoxia, severe hypoxia, normoxia and vascular steal), depending on the carbogen‐induced change in R 1 and R 2 * values for each voxel. The results showed that 9L–gliomas present more normoxic fractions, whereas rhabdomyosarcomas present more hypoxic fractions, which is in accordance with a previous study using 18 F–fluoroazomycin arabinoside ( 18 F–FAZA) and electron paramagnetic resonance (EPR) oximetry. The response of the combined endogenous MRI contrasts to carbogen challenge could be a useful tool to predict different tumor hypoxic fractions. Abstract : We used endogenous magnetic resonance imaging (MRI) contrasts R 1 and R 2 * to follow the carbogen‐induced changes in tumor oxygenation in two rat tumor models. Different types of voxel behavior were observed and classified into four types of hypoxic features, based on Δ R 1 and Δ R 2 * in each voxel. The normoxic fraction was higher in 9L–gliomas, whereas the hypoxic fraction was higher in rhabdomyosarcomas. The response of the combined R 1 ‐ R 2 * to carbogen challenge could be a useful tool to predict different tumor hypoxic fractions.