Purpose-Tumor hypoxia has long been known to produce resistance to radiation. In this study, electron paramagnetic resonance (EPR) oxygen imaging was investigated for its power to predict the success of tumor control depending on tumor oxygenation level and radiation therapy dose.Methods and Materials-Thirty-four EPR oxygen images were obtained from the legs of C3H mice bearing 0.5 ml FSa fibrosarcomas under both normal (air breathing) and clamped tumor conditions. Under the same conditions as those during which the images were obtained, tumors were irradiated to a variety doses near the FSa TCD 50 . Tumor tissue was distinguished from normal tissue using co-registration of the EPR oxygen images with spin-echo MRI images of the tumor and/or stereotactic localization. Tumor voxel statistics in the EPR oxygen image included mean and median pO 2 , and the fraction of tumor voxels below the specified pO 2 values of 3, 6 and 10 torr. Bivariate logistic regression analysis using radiation dose and each of the EPR oxygen image statistics determined which best separated treatment failure from success.Results and Conclusions-TCD 50 measurements were similar to those found in the literature for this syngeneic tumor. Bivariate analysis of 34 tumors demonstrated that tumor cure correlated with dose (p=0.004) and with <10 torr hypoxic fraction (p=0.023). Together, radiation dose and EPR image hypoxic fraction separate the population of FSa fibrosarcomas which are cured from those which fail, thus predicting curability.
Purpose: Application of in vivo electron paramagnetic resonance ͑EPR͒ oxygen imaging ͑EPROI͒ to tumors larger than those of mice requires development of both instrumental and medical aspects of imaging. Methods: 250 MHz EPR oxygen imaging was performed using a loop-gap resonator with a volume exceeding 100 cm 3 . The paramagnetic spin probe was injected directly into the femoral artery feeding the rabbit leg/tumor. Results: The authors present continuous wave and electron spin echo EPR oxygen images of a large size ͑4 cm͒ VX-2 tumor located on the leg of a New Zealand white rabbit. Conclusions: This study demonstrates the feasibility of continuous wave and electron spin echo oxygen imaging modalities for investigation of volumes of tumor and normal tissue relevant to large animals. The injection of the spin probe directly into the artery feeding a rabbit leg will allow one to reduce, by over one order of magnitude, the amount of spin probe used as compared to whole animal IV injection.
PurposeTumor microenvironments show remarkable tumor pO2 heterogeneity, as seen in prior EPR pO2 images (EPROI). pO2 correlation with hypoxia response proteins is frustrated by large rapid pO2 changes with position.ProceduresTo overcome this limitation, biopsies stereotactically located in the EPROI were used to explore the relationship between vascular endothelial growth factor A (VEGF) concentrations in living mouse tumors and the local EPROI pO2.ResultsQuantitative ELISA VEGF concentrations correlated (p = 0.0068 to 0.019) with mean pO2, median pO2, and the fraction of voxels in the biopsy volume with pO2 less than 3, 6, and 10 Torr.ConclusionsThis validates EPROI hypoxic fractions at the molecular level and provides a new paradigm for the assessment of the relationship, in vivo, between hypoxia and hypoxia response proteins. When translated to human subjects, this will enhance understanding of human tumor pathophysiology and cancer response to therapy.
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