title: Assessment of the changes in 9L and C6 glioma pO2 by EPR oximetry as a prognostic indicator of differential response to radiotherapy.
abstract: Tumor hypoxia impedes the outcome of radiotherapy. As the extent of hypoxia in solid tumors varies during the course of radiotherapy, methods that can provide repeated assessment of tumor pO2 such as EPR oximetry may enhance the efficacy of radiotherapy by scheduling irradiations when the tumors are oxygenated. The repeated measurements of tumor pO2 may also identify responders, and thereby facilitate the design of better treatment plans for nonresponding tumors. We have investigated the temporal changes in the ectopic 9L and C6 glioma pO2 irradiated with single radiation doses less than 10 Gy by EPR oximetry. The 9L and C6 tumors were hypoxic with pO2 of approximately 5-9 mmHg. The pO2 of C6 tumors increased significantly with irradiation of 4.8-9.3 Gy. However, no change in the 9L tumor pO2 was observed. The irradiation of the oxygenated C6 tumors with a second dose of 4.8 Gy resulted in a significant delay in growth compared to hypoxic and 2 Gy × 5 treatment groups. The C6 tumors with an increase in pO2 of greater than 50% from the baseline of irradiation with 4.8 Gy (responders) had a significant tumor growth delay compared to nonresponders. These results indicate that the ectopic 9L and C6 tumors responded differently to radiotherapy. We propose that the repeated measurement of the oxygen levels in the tumors during radiotherapy can be used to identify responders and to design tumor oxygen guided treatment plans to improve the outcome.
authors: EPR Center for Viable Systems, Department of Radiology, Geisel School of Medicine, Hanover, New Hampshire, USA.
authors: Huagang
authors: H
authors: Hou
authors: Sriram P
authors: SP
authors: Mupparaju
authors: Jean P
authors: JP
authors: Lariviere
authors: Sassan
authors: S
authors: Hodge
authors: Jiang
authors: J
authors: Gui
authors: Harold M
authors: HM
authors: Swartz
authors: Nadeem
authors: N
authors: Khan
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000532:radiotherapy*; D004578:Electron Spin Resonance Spectroscopy; D005910:Glioma / Q000378:metabolism / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010092:Oximetry / Q000379:methods*; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley
references: Cancer Metastasis Rev. 2007 Jun;26(2):225-39
references: 17440684
references: Cancer Res. 1996 Mar 1;56(5):964-68
references: 8640786
references: Adv Exp Med Biol. 2011;701:107-13
references: 21445776
references: Clin Cancer Res. 2005 Jan 15;11(2 Pt 1):835-42
references: 15701874
references: Antioxid Redox Signal. 2007 Oct;9(10):1691-8
references: 17678442
references: NMR Biomed. 2004 Aug;17(5):335-51
references: 15366033
references: Magn Reson Med. 2002 Oct;48(4):723-30
references: 12353291
references: Radiat Res. 1980 Dec;84(3):529-41
references: 7454994
references: Phys Med Biol. 2004 Oct 7;49(19):4463-75
references: 15552411
references: Int J Radiat Biol. 2010 Feb;86(2):164-73
references: 20148701
references: Radiother Oncol. 2008 Mar;86(3):354-60
references: 18077029
references: Int J Radiat Oncol Biol Phys. 1999 Aug 1;45(1):119-26
references: 10477015
references: J Magn Reson. 2012 Jan;214(1):22-8
references: 22033225
references: Biochim Biophys Acta. 2001 Aug 31;1551(1):M19-27
references: 11553418
references: Radiat Res. 2006 Mar;165(3):326-36
references: 16494521
references: Magn Reson Med. 2007 May;57(5):950-9
references: 17457861
references: Radiat Res. 1998 Nov;150(5):549-56
references: 9806597
references: Br J Radiol. 2000 Aug;73(872):892-4
references: 11026867
references: Br J Radiol. 1979 Aug;52(620):650-6
references: 486895
references: Radiother Oncol. 2012 Oct;105(1):14-20
references: 23083497
references: Int J Radiat Oncol Biol Phys. 1988 Nov;15(5):1187-92
references: 3141321
references: Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):878-85
references: 19136221
references: Cancer Res. 1992 Sep 1;52(17):4620-7
references: 1511430
references: Int J Radiat Oncol Biol Phys. 1994 Jun 15;29(3):493-7
references: 8005805
references: Radiother Oncol. 2009 Apr;91(1):126-31
references: 19013657
references: Radiology. 1972 Oct;105(1):135-42
references: 4506641
references: Adv Exp Med Biol. 1998;454:243-52
references: 9889898
references: Int J Radiat Oncol Biol Phys. 2008 Jun 1;71(2):542-9
references: 18474313
references: J Radiat Res. 2004 Jun;45(2):303-8
references: 15304974
references: J Radiat Res. 2011;52(5):568-74
references: 21799293
references: Adv Exp Med Biol. 2010;662:149-56
references: 20204785
references: Int J Radiat Oncol Biol Phys. 1995 Aug 30;33(1):111-8
references: 7642408
references: Adv Exp Med Biol. 1984;180:773-82
references: 6534148
references: Cancer J. 2006 Nov-Dec;12(6):461-6
references: 17207315
references: Radiat Res. 2003 May;159(5):621-31
references: 12710873
references: Strahlenther Onkol. 1999 Jun;175 Suppl 2:52-6
references: 10394398
references: Radiat Res. 2010 May;173(5):651-8
references: 20426665
references: Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5438-42
references: 8390665
references: Int J Radiat Biol. 1997 Jun;71(6):681-94
references: 9246183
references: Int J Radiat Oncol Biol Phys. 2010 Aug 1;77(5):1500-8
references: 20637978
references: J Neurooncol. 2008 Jan;86(1):13-21
references: 17611717
references: Oncologist. 2008;13 Suppl 3:21-6
references: 18458121
references: Magn Reson Med. 1993 Aug;30(2):213-20
references: 8396190
references: J Appl Physiol (1985). 1997 Jun;82(6):1939-45
references: 9173962
references: Antioxid Redox Signal. 2007 Aug;9(8):1169-82
references: 17536960
references: Radiat Res. 2007 Aug;168(2):218-25
references: 17638413
references: Semin Radiat Oncol. 1996 Jan;6(1):37-45
references: 10717160
references: Int J Radiat Oncol Biol Phys. 1994 Jun 15;29(3):487-91
references: 8005804
references: Oncol Rep. 2011 Jul;26(1):281-6
references: 21503586
references: Curr Pharm Biotechnol. 2012 Mar;13(4):552-70
references: 22214501
references: Acta Oncol. 1999;38(8):1037-42
references: 10665759
references: Int J Radiat Biol. 1999 Apr;75(4):505-12
references: 10331856
references: J Neurooncol. 2009 Sep;94(3):299-312
references: 19381449
references: J Nucl Med. 2012 Aug;53(8):1171-4
references: 22789676
references: Int J Cancer. 1995 May 29;61(5):732-7
references: 7768649
references: Methods. 2003 Jun;30(2):159-66
references: 12725782
references: Onkologie. 2004 Feb;27(1):83-90
references: 15007254
references: Nat Rev Cancer. 2008 Dec;8(12):967-75
references: 18987634
references: Cancer Res. 2003 Mar 1;63(5):1025-33
references: 12615718