Assessment of the Changes in 9L and C6 Glioma pO₂by EPR Oximetry as a Prognostic Indicator of Differential Response to Radiotherapy

Abstract

Tumor hypoxia impedes the outcome of radiotherapy. As the extent of hypoxia in solid tumors varies during the course of radiotherapy, methods that can provide repeated assessment of tumor pO2 such as EPR oximetry may enhance the efficacy of radiotherapy by scheduling irradiations when the tumors are oxygenated. The repeated measurements of tumor pO2 may also identify responders, and thereby facilitate the design of better treatment plans for nonresponding tumors. We have investigated the temporal changes in the ectopic 9L and C6 glioma pO2 irradiated with single radiation doses less than 10 Gy by EPR oximetry. The 9L and C6 tumors were hypoxic with pO2 of approximately 5–9 mmHg. The pO2 of C6 tumors increased significantly with irradiation of 4.8–9.3 Gy. However, no change in the 9L tumor pO2 was observed. The irradiation of the oxygenated C6 tumors with a second dose of 4.8 Gy resulted in a significant delay in growth compared to hypoxic and 2 Gy × 5 treatment groups. The C6 tumors with an increase in pO2 of greater than 50% from the baseline of irradiation with 4.8 Gy (responders) had a significant tumor growth delay compared to nonresponders. These results indicate that the ectopic 9L and C6 tumors responded differently to radiotherapy. We propose that the repeated measurement of the oxygen levels in the tumors during radiotherapy can be used to identify responders and to design tumor oxygen guided treatment plans to improve the outcome.

Skeletal Muscle and Glioma Oxygenation by Carbogen Inhalation in Rats: A Longitudinal Study by EPR Oximetry Using Single-Probe Implantable Oxygen Sensors

“…The ectopic 9L tumors were hypoxic, which are consistent with the earlier reports [4]. However, the response of individual 9L tumors to carbogen varied among the animals.…”

Monitoring oxygen levels in orthotopic human glioma xenograft following carbogen inhalation and chemotherapy by implantable resonator‐based oximetry

“…The anesthetized mice (1.5% isoflurane in 30% O 2 ) were positioned in the EPR magnet and the external surface loop resonator was gently placed over the head region. A magnetic field gradient of 3.0 G/cm was used to separate the EPR spectra from each sensory tip 14, 15 . The peak-to-peak line-widths of the EPR spectra were used to determine pO 2 by using the calibration of each implantable resonator.…”

“…The goal of this study was to demonstrate pO 2 measurements in both hemispheres of mouse brain by using implantable resonators with multi-site EPR oximetry. The multi-site oximetry approach involves the use of magnetic field gradients for simultaneous measurement of pO 2 at two or more sites in a tissue of interest 12, 14, 15 . The oximetry technique with implantable resonators was used to investigate temporal changes in the cerebral pO 2 of control mice and those inoculated with U251 glioma and the response to carbogen inhalation for hyperoxygenation.…”

Imaging Tumor Hypoxia to Advance Radiation Oncology

“…To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars 107) and to examine changes in tumor oxygenation in response to vascular changes (6,111). Recently, it was demonstrated using EPR oximetry that ectopic C6 glioma tumors grown in mice had significantly increased pO 2 after irradiation, and this corresponded with prolonged tumor growth delay (107). In fact, clinical EPR spectrometers have been built that may permit the eventual use of EPR oximetry in clinical trials (118,213,234).…”