title: Intracellular hypoxia of tumor tissue estimated by noninvasive electron paramagnetic resonance oximetry technique using paramagnetic probes.
abstract: Electron paramagnetic resonance (EPR) oximetry at 700 MHz operating frequency employing a surface coil resonator is used to assess tissue partial pressure of oxygen (pO(2)) using paramagnetic media whose linewidth and decay constant are related to oxygen concentration. Differences in extracellular and intracellular pO(2) in squamous cell carcinoma (SCC) tumor tissue were tested using several types of water-soluble paramagnetic media, which localize extracellularly or permeate through the cell membrane. The nitroxide carboxy-PROXYL (CxP) can only be distributed in blood plasma and extracellular fluids whereas the nitroxides carbamoyl-PROXYL (CmP) and TEMPOL (TPL) can permeate cell membranes and localize intracellularly. EPR signal decay constant and the linewidth of the intravenously administered nitroxides in SCC tumor tissues implanted in mouse thigh and the contralateral normal muscle of healthy mice breathing gases with different pO(2) were compared. The pO(2) in the blood can depend on the oxygen content in the breathing gas while tissue pO(2) was not directly influenced by pO(2) in the breathing gas. The decay constants of CmP and TPL in tumor tissue were significantly larger than in the normal muscles, and lower linewidths of CmP and TPL in tumor tissue was observed. The SCC tumor showed intracellular hypoxia even though the extracellular pO(2) is similar to normal tissue in the peripheral region.
authors.affiliation: Radiation Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892–1002, USA.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Fuminori
authors.initials: F
authors.lastname: Hyodo
authors.forename: Anastasia L
authors.initials: AL
authors.lastname: Sowers
authors.forename: Janusz W
authors.initials: JW
authors.lastname: Koscielniak
authors.forename: Nallathamby
authors.initials: N
authors.lastname: Devasahayam
authors.forename: Sankaran
authors.initials: S
authors.lastname: Subramanian
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Murali C
authors.initials: MC
authors.lastname: Krishna
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000098:blood supply; D010092:Oximetry / Q000379:methods*; D010100:Oxygen / Q000378:metabolism*; D010313:Partial Pressure; D013113:Spin Labels
chemical_list: D013113:Spin Labels; D010100:Oxygen