Monitoring Tumor Response to Carbogen Breathing by Oxygen-Sensitive Magnetic Resonance Parameters to Predict the Outcome of Radiation Therapy: A Preclinical Study

Purpose In an effort to develop noninvasive in vivo methods for mapping tumor oxygenation, magnetic resonance (MR)-derived parameters are being considered, including global R1 , water R1 , lipids R1 , and R2 *. R1 is sensitive to dissolved molecular oxygen, whereas R2 * is sensitive to blood oxygenation, detecting changes in dHb. This work compares global R1 , water R1 , lipids R1 , and R2 * with pO2 assessed by electron paramagnetic resonance (EPR) oximetry, as potential markers of the outcome of radiation therapy (RT). Methods and Materials R1 , R2 *, and EPR were performed on rhabdomyosarcoma and 9L-glioma tumor models, under air and carbogen breathing conditions (95% O2 , 5% CO2 ). Because the models demonstrated different radiosensitivity properties toward carbogen, a growth delay (GD) assay was performed on the rhabdomyosarcoma model and a tumor control dose 50% (TCD50) was performed on the 9L-glioma model. Results Magnetic resonance imaging oxygen-sensitive parameters detected the positive changes in oxygenation induced by carbogen within tumors. No consistent correlation was seen throughout the study between MR parameters and pO2 . Global and lipids R1 were found to be correlated to pO2 in the rhabdomyosarcoma model, whereas R2 * was found to be inversely correlated to pO2 in the 9L-glioma model ( P =.05 and .03). Carbogen increased the TCD50 of 9L-glioma but did not increase the GD of rhabdomyosarcoma. Only R2 * was predictive ( P