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Clinical Studies

EPR Oxygen Images Predict Tumor Control by a 50% Tumor Control Radiation Dose

Martyna Elas, Jessica M. Magwood, Brandi Butler, Chanel Li, Rona Wardak, Eugene D. Barth, Boris Epel, Samuel Rubinstein, Charles A. Pelizzari, Ralph R. Weichselbaum and Howard J. Halpern
Martyna Elas
Authors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandAuthors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandAuthors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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Jessica M. Magwood
Authors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandAuthors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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Brandi Butler
Authors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandAuthors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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Chanel Li
Authors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandAuthors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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Rona Wardak
Authors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandAuthors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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Eugene D. Barth
Authors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandAuthors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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Boris Epel
Authors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandAuthors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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Samuel Rubinstein
Authors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandAuthors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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Charles A. Pelizzari
Authors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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Ralph R. Weichselbaum
Authors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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Howard J. Halpern
Authors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandAuthors' Affiliations: Departments of Radiation and Cellular Oncology and Radiology, Pritzker School of Medicine; Center for Electron Paramagnetic Resonance Imaging In Vivo Physiology, University of Chicago, Chicago, Illinois; and Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland
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DOI: 10.1158/0008-5472.CAN-13-0069
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Abstract

Clinical trials to ameliorate hypoxia as a strategy to relieve the radiation resistance it causes have prompted a need to assay the precise extent and location of hypoxia in tumors. Electron paramagnetic resonance oxygen imaging (EPR O2 imaging) provides a noninvasive means to address this need. To obtain a preclinical proof-of-principle that EPR O2 images could predict radiation control, we treated mouse tumors at or near doses required to achieve 50% control (TCD50). Mice with FSa fibrosarcoma or MCa4 carcinoma were subjected to EPR O2 imaging and immediately radiated to a TCD50 or TCD50 ± 10 Gy. Statistical analysis was permitted by collection of approximately 1,300 tumor pO2 image voxels, including the fraction of tumor voxels with pO2 less than 10 mm Hg (HF10). Tumors were followed for 90 days (FSa) or 120 days (MCa4) to determine local control or failure. HF10 obtained from EPR images showed statistically significant differences between tumors that were controlled by the TCD50 and those that were not controlled for both FSa and MCa4. Kaplan–Meier analysis of both types of tumors showed that approximately 90% of mildly hypoxic tumors were controlled (HF10%< 10%), and only 37% (FSA) and 23% (MCa4) tumors controlled if hypoxic. EPR pO2 image voxel distributions in these approximately 0.5 mL tumors provide a prediction of radiation curability independent of radiation dose. These data confirm the significance of EPR pO2 hypoxic fractions. The 90% control of low HF10 tumors argue that 0.5 mL subvolumes of tumors may be more sensitive to radiation and may need less radiation for high tumor control rates. Cancer Res; 73(17); 1–8. ©2013 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received January 8, 2013.
  • Revision received May 7, 2013.
  • Accepted May 25, 2013.
  • ©2013 American Association for Cancer Research.
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Published OnlineFirst August 23, 2013
doi: 10.1158/0008-5472.CAN-13-0069

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EPR Oxygen Images Predict Tumor Control by a 50% Tumor Control Radiation Dose
Martyna Elas, Jessica M. Magwood, Brandi Butler, Chanel Li, Rona Wardak, Eugene D. Barth, Boris Epel, Samuel Rubinstein, Charles A. Pelizzari, Ralph R. Weichselbaum and Howard J. Halpern
Cancer Res August 23 2013 DOI: 10.1158/0008-5472.CAN-13-0069

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EPR Oxygen Images Predict Tumor Control by a 50% Tumor Control Radiation Dose
Martyna Elas, Jessica M. Magwood, Brandi Butler, Chanel Li, Rona Wardak, Eugene D. Barth, Boris Epel, Samuel Rubinstein, Charles A. Pelizzari, Ralph R. Weichselbaum and Howard J. Halpern
Cancer Res August 23 2013 DOI: 10.1158/0008-5472.CAN-13-0069
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