O'Connor, J. P. B., Boult, J. K. R., Jamin, Y., Babur, M., Finegan, K. G., Williams, K. J., Little, R. A., Jackson, A., Parker, G. J. M., Reynolds, A. R., Waterton, J. C., Robinson, S. P. (2016) Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models. CANCER RESEARCH, 76 (4). pp. 787-795. ISSN 0008-5472

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Abstract

There is a clinical need for noninvasive biomarkers of tumor hypoxia for prognostic and predictive studies, radiotherapy planning, and therapy monitoring. Oxygen-enhanced MRI (OE-MRI) is an emerging imaging technique for quantifying the spatial distribution and extent of tumor oxygen delivery in vivo. In OE-MRI, the longitudinal relaxation rate of protons (Delta R-1) changes in proportion to the concentration of molecular oxygen dissolved in plasma or interstitial tissue fluid. Therefore, well-oxygenated tissues show positive Delta R-1. We hypothesized that the fraction of tumor tissue refractory to oxygen challenge (lack of positive Delta R-1, termed "Oxy-R fraction") would be a robust biomarker of hypoxia in models with varying vascular and hypoxic features. Here, we demonstrate that OE-MRI signals are accurate, precise, and sensitive to changes in tumor pO(2) in highly vascular 786-0 renal cancer xenografts. Furthermore, we show that Oxy-R fraction can quantify the hypoxic fraction in multiple models with differing hypoxic and vascular phenotypes, when used in combination with measurements of tumor perfusion. Finally, OxyR fraction can detect dynamic changes in hypoxia induced by the vasomodulator agent hydralazine. In contrast, more conventional biomarkers of hypoxia (derived from blood oxygenation-level dependent MRI and dynamic contrast-enhanced MRI) did not relate to tumor hypoxia consistently. Our results show that the Oxy-R fraction accurately quantifies tumor hypoxia noninvasively and is immediately translatable to the clinic. (C) 2015 AACR.

Item Type:	Article
Authors (ICR Faculty only):	Reynolds, Andy and Robinson, Simon
All Authors:	O'Connor, J. P. B., Boult, J. K. R., Jamin, Y., Babur, M., Finegan, K. G., Williams, K. J., Little, R. A., Jackson, A., Parker, G. J. M., Reynolds, A. R., Waterton, J. C., Robinson, S. P.
Additional Information:	ISI Document Delivery No.: DD7UI Times Cited: 1 Cited Reference Count: 50 O'Connor, James P. B. Boult, Jessica K. R. Jamin, Yann Babur, Muhammad Finegan, Katherine G. Williams, Kaye J. Little, Ross A. Jackson, Alan Parker, Geoff J. M. Reynolds, Andrew R. Waterton, John C. Robinson, Simon P. Cancer Research UK (CRUK) Clinician Scientist award [C19221/A15267]; CRUK; EPSRC Cancer Imaging Centre in Cambridge and Manchester [C8742/A18097]; CRUK Cancer Imaging Centre [C1060/A10334, C1060/A16464]; Wellcome Trust [091763Z/10/Z]; Children with Cancer UK [2014/176]; Breakthrough Breast Cancer Senior Fellowship This study was supported by Cancer Research UK (CRUK) Clinician Scientist award (grant C19221/A15267 to J.P.B. O'Connor), CRUK and EPSRC Cancer Imaging Centre in Cambridge and Manchester funding to The University of Manchester (grant C8742/A18097 to J.P.B. O'Connor, K.J. Williams, A. Jackson, and G.J.M. Parker), CRUK Cancer Imaging Centre funding to The Institute of Cancer Research (grants C1060/A10334 and C1060/A16464 to S.P. Robinson), The Wellcome Trust funding (grant 091763Z/10/Z to S.P. Robinson), Paul O'Gorman Postdoctoral Fellowship funded by Children with Cancer UK (grant 2014/176; Y. Jamin), and Breakthrough Breast Cancer Senior Fellowship (A.R. Reynolds). Breakthrough Breast Cancer has recently merged with Breast Cancer Campaign to form Breast Cancer Now. 1 0 Amer assoc cancer research Philadelphia 1538-7445
Uncontrolled Keywords:	imaging biomarkers tissue oxygenation pet tracers contrast therapy blood qualification heterogeneity radiotherapy angiogenesis Oncology
Research teams:	ICR divisions > Radiotherapy and Imaging > Magnetic Resonance Closed research groups > Tumour Biology
Depositing User:	Franziska Noessig
Date Deposited:	14 Mar 2016 17:39
Last Modified:	25 Apr 2017 15:30
URI:	http://publications.icr.ac.uk/id/eprint/14871

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