Tissue pO2 of Orthotopic 9L and C6 Gliomas and Tumor-Specific Response to Radiotherapy and Hyperoxygenation
Received 17 July 2008; received in revised form 7 October 2008; accepted 8 October 2008. published online 12 January 2009.
Purpose
Tumor hypoxia is a well-known therapeutic problem; however, a lack of methods for repeated measurements of glioma partial pressure of oxygen (pO2) limits the ability to optimize the therapeutic approaches. We report the effects of 9.3 Gy of radiation and carbogen inhalation on orthotopic 9L and C6 gliomas and on the contralateral brain pO2 in rats using a new and potentially widely useful method, multisite in vivo electron paramagnetic resonance oximetry.
Methods and Materials
Intracerebral 9L and C6 tumors were established in the left hemisphere of syngeneic rats, and electron paramagnetic resonance oximetry was successfully used for repeated tissue pO2 measurements after 9.3 Gy of radiation and during carbogen breathing for 5 consecutive days.
Results
Intracerebral 9L gliomas had a pO2 of 30–32 mm Hg and C6 gliomas were relatively hypoxic, with a pO2 of 12–14 mm Hg (p < 0.05). The tissue pO2 of the contralateral brain was 40–45 mm Hg in rats with either 9L or C6 gliomas. Irradiation resulted in a significant increase in pO2 of the 9L gliomas only. A significant increase in the pO2 of the 9L and C6 gliomas was observed in rats breathing carbogen, but this effect decreased during 5 days of repeated experiments in the 9L gliomas.
Conclusion
These results highlight the tumor-specific effect of radiation (9.3.Gy) on tissue pO2 and the different responses to carbogen inhalation. The ability of electron paramagnetic resonance oximetry to provide direct repeated measurements of tissue pO2 could have a vital role in understanding the dynamics of hypoxia during therapy that could then be optimized by scheduling doses at times of improved tumor oxygenation.
∗EPR Center for Viable Systems, Dartmouth Medical School, Hanover, NH
†Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH
‡Department of Medicine, Section of Radiation Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
Reprint requests to: Nadeem Khan, Ph.D., EPR Center for Viable Systems, 703 Vail, Dartmouth Medical School, Hanover, NH 03755. Tel: (603) 653-3591; Fax: (603) 650-1717
Supported by the National Cancer Institute (Grant CA120919) and National Institutes of Health (Grant PO1EB2180).
ABSTRACT