Differentiation between hypoxic and non-hypoxic experimental tumors by dynamic contrast-enhanced magnetic resonance imaging.

Abstract

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has been suggested to be a useful method for detecting tumor hypoxia. In this study, we investigated whether DCE-MRI can differentiate between hypoxic and non-hypoxic experimental tumors. Three tumor models with hypoxic tissue and three tumor models without hypoxic tissue were subjected to DCE-MRI. Parametric images of K(trans) (the volume transfer constant of Gd-DTPA) and v(e) (the fractional distribution volume of Gd-DTPA) were produced by pharmacokinetic analysis of the DCE-MRI series. Tumor oxygenation status was assessed by using a radiobiological assay and a pimonidazole-based immunohistochemical assay. Tumor response to fractionated irradiation (six fractions of 2Gy in 60h) was measured in vitro by using a clonogenic assay. Tumors with hypoxic regions were more resistant to radiation treatment than were tumors without hypoxia. K(trans) was significantly higher for radiation sensitive tumors without hypoxia than for radiation resistant tumors with hypoxic regions, whereas v(e) did not differ significantly between non-hypoxic and hypoxic tumors. This study supports the clinical attempts to establish DCE-MRI as a noninvasive method for providing useful biomarkers for personalized radiation therapy.