Oxygen-Sensitive MRI: A Predictive Imaging Biomarker for Tumor Radiation Response?

Purpose: To develop a noninvasive prognostic imaging biomarker related to hypoxia to predict SABR tumor control. Methods and Materials: A total of 145 subcutaneous syngeneic Dunning prostate R3327-AT1 rat tumors were focally irradiated once using cone beam computed tomography guidance on a small animal irradiator at 225 kV. Various doses in the range of 0 to 100 Gy were administered, while rats breathed air or oxygen, and tumor control was assessed up to 200 days. Oxygen-sensitive magnetic resonance imaging (MRI) (T-1-weighted, Delta R-1, Delta R-2*) was applied to 79 of these tumors at 4.7 T to assess response to an oxygen gas breathing challenge on the day before irradiation as a probe of tumor hypoxia. Results: Increasing radiation dose in the range of 0 to 90 Gy enhanced tumor control of air-breathing rats with a TCD50 estimated at 59.6 +/- 1.5 Gy. Control was significantly improved at some doses when rats breathed oxygen during irradiation (eg, 40 Gy; P<.05), and overall there was a modest left shift in the control curve: TCD50(oxygen) = 53.1 +/- 3.1 Gy (P<.05 vs air). Oxygen-sensitive MRI showed variable response to oxygen gas breathing challenge; the magnitude of T-1-weighted signal response (%DSI) allowed stratification of tumors in terms of local control at 40 Gy. Tumors showing %Delta SI >0.922 with O-2-gas breathing challenge showed significantly better control at 40 Gy during irradiation while breathing oxygen (75% vs 0%, P<.01). In addition, increased radiation dose (50 Gy) substantially overcame resistance, with 50% control for poorly oxygenated tumors. Stratification of dose-response curves based on %Delta SI >0.922 revealed different survival curves, with TCD50 = 36.2 +/- 3.2 Gy for tumors responsive to oxygen gas breathing challenge; this was significantly less than the 54.7 +/- 2.4 Gy for unresponsive tumors (P<.005), irrespective of the gas inhaled during tumor irradiation. Conclusions: Oxygen-sensitive MRI allowed stratification of tumors in terms of local control at 40 Gy, indicating its use as a potential predictive imaging biomarker. Increasing dose to 50 Gy overcame radiation resistance attributable to hypoxia in 50% of tumors. (C) 2021 Elsevier Inc. All rights reserved.