Effect of hyperoxygenation on tissue pO2 and its effect on radiotherapeutic efficacy of orthotopic F98 gliomas.
OBJECTIVE
Lack of methods for repeated assessment of tumor pO(2) limits the ability to test and optimize hypoxia-modifying procedures being developed for clinical applications. We report repeated measurements of orthotopic F98 tumor pO(2) and relate this to the effect of carbogen inhalation on tumor growth when combined with hypofractionated radiotherapy.


METHODS
Electron paramagnetic resonance (EPR) oximetry was used for repeated measurements of tumor and contralateral brain pO(2) in rats during 30% O(2) and carbogen inhalation for 5 consecutive days. The T(1)-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% O(2) or carbogen to determine the effect on tumor growth.


RESULTS
The pretreatment F98 tumor pO(2) varied between 8 and 16 mmHg, while the contralateral brain had 41 to 45 mmHg pO(2) during repeated measurements. Carbogen breathing led to a significant increase in tumor and contralateral brain pO(2); 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 pO(2) and its effect on therapeutic outcome. Such direct repeated pO(2) 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.
Khan
Nadeem
N
EPR Center for Viable Systems, Dartmouth Medical School, Hanover, NH 03755, USA. Nadeem.khan@dartmouth.edu
Mupparaju
Sriram
S
Hekmatyar
Shahryar K
SK
Hou
Huagang
H
Lariviere
Jean P
JP
Demidenko
Eugene
E
Gladstone
David J
DJ
Kauppinen
Risto A
RA
Swartz
Harold M
HM
D000818:Animals; D001932:Brain Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy; D002245:Carbon Dioxide / Q000008:administration & dosage*; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D004334:Drug Administration Schedule; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005910:Glioma / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy; D008279:Magnetic Resonance Imaging; D010092:Oximetry / Q000379:methods*; D010100:Oxygen / Q000008:administration & dosage / Q000032:analysis*; D010313:Partial Pressure; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D011879:Radiotherapy Dosage; D011897:Random Allocation; D051381:Rats; D047368:Tumor Burden
D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen
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