Electron Paramagnetic Resonance (EPR) Oxygen Images (EPROI) provide quantitative localized pO2 distributions in animal tumors of syngeneic mice, rats, and rabbits. The oxygen broadening of narrow EPR spectral lines reports the pO2 with 1-3 torr resolution in each 1mm3 image voxel. This work has successfully shown 1) the first co-localized correlation between an oxygen image and a point oxygen measurement technique (Oxylite);2) independent, statistically significant sharpening of the 50% tumor control dose with the addition of the information provided by the fraction of EPROI voxels with pO2 less than 10 torr (HF10);3) significant spatial correlation of VEGF and EPROI based HF10;4) when treated to the dose necessary to control 50% (TCD50) of all FSa fibrosarcomas, control is only 28% in tumors with HF10>8% while it increases to 92% for those with HF10<8%. In the next funding cycle we propose to explore EPROI as the basis for IMRT dose painting in 2cm rat 13762 carcinomas, chosen for ease of IMRT via increased size. We propose the following specific aims for the next funding cycle: exploring the effectiveness of 1) Adding a fixed dose to the TCD50 targeting an IMRT boost to an EPROI based hypoxic region, compared with adding the same boost dose to a well oxygenated tumor region of equal volume 2) Adding dose to the hypoxic region and reduced dose to a well oxygenated region. This would be compared with delivery of uniform TCD50. 3) Adding a graded dose to regions of the tumor proportional to the HF10. This work will test the efficacy of the use of oxygen imaging in dose painting in small mammals. It will provide a path to enhancement of radiation therapy efficacy and reduction of its side effects.

Public Health Relevance

This work continues the investigation of a new technique to predict cure likelihood using radiation therapy for cancers and to improve the cure of cancers with radiation. The technique involves a non-invasive electron magnetic resonance image of a non-toxic compound, injected in an animal, which reports the amount of oxygen in each of the 1 mm3 volumes of the animal tumor. This eventually will guide the placement of extra radiation dose to enhance human tumor treatment with radiation.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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Radiation Therapeutics and Biology Study Section (RTB)
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Bernhard, Eric J
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University of Chicago
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Redler, Gage; Epel, Boris; Halpern, Howard J (2014) EPR image based oxygen movies for transient hypoxia. Adv Exp Med Biol 812:127-33
Redler, Gage; Epel, Boris; Halpern, Howard J (2014) Principal component analysis enhances SNR for dynamic electron paramagnetic resonance oxygen imaging of cycling hypoxia in vivo. Magn Reson Med 71:440-50
Epel, Boris; Redler, Gage; Halpern, Howard J (2014) How in vivo EPR measures and images oxygen. Adv Exp Med Biol 812:113-9
Epel, Boris; Bowman, Michael K; Mailer, Colin et al. (2014) Absolute oxygen R1e imaging in vivo with pulse electron paramagnetic resonance. Magn Reson Med 72:362-8
Redler, Gage; Epel, Boris; Halpern, Howard J (2014) What we learn from in vivo EPR oxygen images. Adv Exp Med Biol 812:121-6
Redler, Gage; Barth, Eugene D; Bauer Jr, Kenneth S et al. (2014) In vivo electron paramagnetic resonance imaging of differential tumor targeting using cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl. Magn Reson Med 71:1650-6
Sundramoorthy, Subramanian V; Epel, Boris; Halpern, Howard J (2014) Orthogonal resonators for pulse in vivo electron paramagnetic imaging at 250 MHz. J Magn Reson 240:45-51
Elas, Martyna; Magwood, Jessica M; Butler, Brandi et al. (2013) EPR oxygen images predict tumor control by a 50% tumor control radiation dose. Cancer Res 73:5328-35
Redler, Gage; Elas, Martyna; Epel, Boris et al. (2013) Radiation oxygen biology with pulse electron paramagnetic resonance imaging in animal tumors. Adv Exp Med Biol 789:399-404
Epel, Boris; Sundramoorthy, Subramanian V; Barth, Eugene D et al. (2011) Comparison of 250 MHz electron spin echo and continuous wave oxygen EPR imaging methods for in vivo applications. Med Phys 38:2045-52

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