International Journal of Radiation Oncology * Biology * Physics
Volume 78, Issue 4 , Pages 1193-1200, 15 November 2010

Effect of Hyperoxygenation on Tissue pO2 and Its Effect on Radiotherapeutic Efficacy of Orthotopic F98 Gliomas

  • Nadeem Khan, Ph.D.

      Affiliations

    • EPR Center for Viable Systems, Dartmouth Medical School, Hanover, New Hampshire
    • Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
    • Corresponding Author InformationReprint 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
    • ,
  • Sriram Mupparaju, M.S.

      Affiliations

    • EPR Center for Viable Systems, Dartmouth Medical School, Hanover, New Hampshire
    • Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
    • ,
  • Shahryar K. Hekmatyar, Ph.D.

      Affiliations

    • Biomedical NMR Research Center, Dartmouth Medical School, Hanover, New Hampshire
    • ,
  • Huagang Hou, M.D.

      Affiliations

    • EPR Center for Viable Systems, Dartmouth Medical School, Hanover, New Hampshire
    • Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
    • ,
  • Jean P. Lariviere, B.A.

      Affiliations

    • EPR Center for Viable Systems, Dartmouth Medical School, Hanover, New Hampshire
    • Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
    • ,
  • Eugene Demidenko, Ph.D.

      Affiliations

    • EPR Center for Viable Systems, Dartmouth Medical School, Hanover, New Hampshire
    • Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
    • ,
  • David J. Gladstone, Sc.D.

      Affiliations

    • Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
    • ,
  • Risto A. Kauppinen, M.D, Ph.D.

      Affiliations

    • Biomedical NMR Research Center, Dartmouth Medical School, Hanover, New Hampshire
    • ,
  • Harold M. Swartz, M.D., Ph.D.

      Affiliations

    • EPR Center for Viable Systems, Dartmouth Medical School, Hanover, New Hampshire
    • Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire

Received 17 November 2009; received in revised form 20 April 2010; accepted 25 May 2010. published online 01 September 2010.

Purpose

Lack of methods for repeated assessment of tumor pO2 limits the ability to test and optimize hypoxia-modifying procedures being developed for clinical applications. We report repeated measurements of orthotopic F98 tumor pO2 and relate this to the effect of carbogen inhalation on tumor growth when combined with hypofractionated radiotherapy.

Methods and Materials

Electron paramagnetic resonance (EPR) oximetry was used for repeated measurements of tumor and contralateral brain pO2 in rats during 30% O2 and carbogen inhalation for 5 consecutive days. The T1-enhanced volumes and diffusion coefficients of the tumors were assessed by magnetic resonance imaging (MRI). The tumors were irradiated with 9.3 Gy x 4 fractions in rats breathing 30% O2 or carbogen to determine the effect on tumor growth.

Results

The pretreatment F98 tumor pO2 varied between 8 and 16 mmHg, while the contralateral brain had 41 to 45 mmHg pO2 during repeated measurements. Carbogen breathing led to a significant increase in tumor and contralateral brain pO2; however, this effect declined over days. Irradiation of the tumors in rats breathing carbogen resulted in a significant decrease in tumor growth and an increase in the diffusion coefficient measured by MRI.

Conclusions

The results provide quantitative measurements of the effect of carbogen inhalation on intracerebral tumor pO2 and its effect on therapeutic outcome. Such direct repeated pO2 measurements by EPR oximetry can provide temporal information that could be used to improve therapeutic outcome by scheduling doses at times of improved tumor oxygenation. EPR oximetry is currently being tested for clinical applications.

F98 glioma, EPR oximetry, MRI, pO2, Radiotherapy

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 30.00 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

 This work was supported by NIH Grants CA120919 and CA118069 to N.K. and PO1EB2180 to H.M.S.

 Conflict of interest: none.

PII: S0360-3016(10)00788-1

doi:10.1016/j.ijrobp.2010.05.045

International Journal of Radiation Oncology * Biology * Physics
Volume 78, Issue 4 , Pages 1193-1200, 15 November 2010

Article Tools

* Image Usage & Resolution