Magnetic Resonance Imaging Approaches for Predicting the Response to Hyperoxic Radiotherapy in Glioma-Bearing Rats

Abstract

Background: Despite the advances in multimodal therapeutic options, glioblastoma (GBM), the most frequent and aggressive of all astrocytomas, remains with a median survival of 15 months. It is reported a direct correlation between GBM hypoxia and a higher aggressiveness, poor prognosis and greater resistance to different treatments. Because of the intratumoral and interindividual heterogeneity, it is not possible to predict the hypoxia degree considering physiopathological parameters or conventional neuroimaging studies. In this study, we aim to develop magnetic resonance imaging (MRI) approaches to identify the tumors that could improve the outcome with an oxygen targeted therapy. Methods: A GBM animal model, obtained by intracranial injection of glioma C6 cells in rats, was employed to assess the efficacy of radiotherapy in animals irradiated under air and oxygen breathing. MRI studies, based on the oxygen induced contrast in blood (BOLD) and tissues (TOLD), were carried out to evaluate the effect of the oxygen modulation in the tumors. The effectiveness of the therapy was determined by the relative volume at the end of the experiment compared to the glioma size the day before the treatment. Results: Obtained results categorized the tumors in responding, non-responding and animals with an intermediate behavior. While BOLD analysis did not show any statistical difference between animals, either breathing air or oxygen, TOLD related parameters allow to identify the tumors with higher response to hyperoxygenic radiotherapy. Conclusions: The non-invasive oxygen enhanced MRI acquisitions proposed, show promising potential to detect those tumors that generally would improve their response to a hypoxia targeted treatment. Our results reveal that the effects of intervention in tumor pO2 cannot be readily predicted based on tumor features, strengthening the necessity of an adequate method to identify tumors that could benefice from an oxygen modulation during treatment.