Synergistic Combination of Hyperoxygenation and Radiotherapy by Repeated Assessments of Tumor pO sub(2) with EPR Oximetry

• Published in: Journal of radiation research Vol. 52; no. 5; pp. 568 - 574
• Main Authors: Hou, Huagang, Dong, Ruhong, Lariviere, Jean P, Mupparaju, Sriram P, Swartz, Harold M, Khan, Nadeem
• Format: Journal Article
• Language: English
• Published: 01.01.2011
• ISSN: 1349-9157
• DOI: 10.1269/jrr.11028

The effect of hyperoxygenation with carbogen (95% O sub(2) + 5% CO sub(2)) inhalation on RIF-1 tumor pO sub(2 )and its consequence on growth inhibition with fractionated radiotherapy is reported. The temporal changes in the tumor pO sub(2) were assessed by in vivo Electron Paramagnetic Resonance (EPR) oximetry in mice breathing 30% O sub(2) or carbogen and the tumors were irradiated with 4 Gy/day for 5 consecutive days; a protocol that emulates the clinical application of carbogen. The RIF-1 tumors were hypoxic with a tissue pO sub(2) of 5-9 mmHg. Carbogen (CB) breathing significantly increased tumor pO sub(2), with a maximum increase at 22.9-31.2 min on days 1-5, however, the magnitude of increase in pO sub(2) declined on day 5. Radiotherapy during carbogen inhalation (CB/RT) resulted in a significant tumor growth inhibition from day 3 to day 6 as compared to 30%O sub(2)/RT and carbogen (CB/Sham RT) groups. The results provide unambiguous quantitative information on the effect of carbogen inhalation on tumor pO sub(2) over the course of 5 days. Tumor growth inhibition in the CB/RT group confirms that the tumor oxygenation with carbogen was radiobiologically significant. Repeated tumor pO sub(2) measurements by EPR oximetry can provide temporal information that could be used to improve therapeutic outcomes by scheduling doses at times of improved tumor oxygenation.