Breathing normobaric carbogen (95% O2/5% CO2) has been shown to increase oxygenation in some tumors, making them more radiation sensitive, and has resulted in improved drug delivery. We have examined two experimental murine tumors for their oxygenation response to carbogen breathing: the radiation-induced fibrosarcoma RIF-1 and the mammary adenocarcinoma MTG-B. Using MR imaging techniques sensitive to hemoglobin oxygenation (Blood Oxygen Level Dependent commonly named BOLD), one can determine non invasively if there is a vascular response to carbogen breathing. A multi-echo FLASH sequence was used on a 7 Tesla magnet to quantify the apparent transverse relaxation time T2* on a pixel by pixel basis. T2* map variation will then reflect deoxyhemoglobin content changes. RIF-1 were also assessed for pO2 using EPR oximetry. A 1.2GHz spectrometer and LiPc crystal as the oxygen sensitive material were used. The EPR oximetry measurements showed little change in pO2 with carbogen breathing in these two tumors. The T2* response with carbogen breathing showed significant variability between and within tumors when the whole tumor was used as a region of interest. In RIF-1 tumors the T2* tended to decrease, an effect which is opposite to that expected if carbogen increased blood oxygenation in the tumor. These tumors appear to exhibit a vascular response which results in increased deoxyhemoglobin with carbogen (due to increased blood volume and/or decreased hemoglobin saturation). Using T2* mapping we can quantify the response of a tumor to carbogen with high spatial resolution. There is a significant inter-tumor variability, and T2* mapping may be able to identify tumors that can be reoxygenated with carbogen. The macroscopic variation provides regional information on tumor oxygenation and vascular regulation.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR011602-05
Application #
6353205
Study Section
Project Start
2000-09-01
Project End
2002-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
5
Fiscal Year
2000
Total Cost
$12,155
Indirect Cost
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
Sinha, Birandra K; Leinisch, Fabian; Bhattacharjee, Suchandra et al. (2014) DNA cleavage and detection of DNA radicals formed from hydralazine and copper (II) by ESR and immuno-spin trapping. Chem Res Toxicol 27:674-82
Dunn, Jeff F; Khan, Mohammad N; Hou, Huagang G et al. (2011) Cerebral oxygenation in awake rats during acclimation and deacclimation to hypoxia: an in vivo electron paramagnetic resonance study. High Alt Med Biol 12:71-7
Shen, Jiangang; Khan, Nadeem; Lewis, Lionel D et al. (2003) Oxygen consumption rates and oxygen concentration in molt-4 cells and their mtDNA depleted (rho0) mutants. Biophys J 84:1291-8
Khan, Nadeem; Wilmot, Carmen M; Rosen, Gerald M et al. (2003) Spin traps: in vitro toxicity and stability of radical adducts. Free Radic Biol Med 34:1473-81
Pogue, Brian W; O'Hara, Julia A; Demidenko, Eugene et al. (2003) Photodynamic therapy with verteporfin in the radiation-induced fibrosarcoma-1 tumor causes enhanced radiation sensitivity. Cancer Res 63:1025-33
Hou, Huagang; Grinberg, Oleg Y; Taie, Satoshi et al. (2003) Electron paramagnetic resonance assessment of brain tissue oxygen tension in anesthetized rats. Anesth Analg 96:1467-72, table of contents
Chen, Bin; Pogue, Brian W; Goodwin, Isak A et al. (2003) Blood flow dynamics after photodynamic therapy with verteporfin in the RIF-1 tumor. Radiat Res 160:452-9
Dunn, Jeff F; Swartz, Harold M (2003) In vivo electron paramagnetic resonance oximetry with particulate materials. Methods 30:159-66
Khan, Nadeem; Shen, Jiangang; Chang, Ta Yuan et al. (2003) Plasma membrane cholesterol: a possible barrier to intracellular oxygen in normal and mutant CHO cells defective in cholesterol metabolism. Biochemistry 42:23-9
Swartz, Harold M (2002) Measuring real levels of oxygen in vivo: opportunities and challenges. Biochem Soc Trans 30:248-52

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