American Association for Cancer Research
00085472can152062-sup-151096_2_supp_3206097_nwzc61.pptx (125.35 kB)

Supplementary Figure S3 from Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models

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posted on 2023-03-30, 23:46 authored by James P.B. O'Connor, Jessica K.R. Boult, Yann Jamin, Muhammad Babur, Katherine G. Finegan, Kaye J. Williams, Ross A. Little, Alan Jackson, Geoff J.M. Parker, Andrew R. Reynolds, John C. Waterton, Simon P. Robinson

R1 changes in Oxy-E and Oxy-R sub-regions


Cancer Research UK (CRUK) Clinician Scientist

CRUK and EPSRC Cancer Imaging Centre in Cambridge and Manchester funding to The University of Manchester

CRUK Cancer Imaging Centre funding to The Institute of Cancer Research

The Wellcome Trust

Paul O'Gorman Postdoctoral Fellowship funded by Children with Cancer UK

Breakthrough Breast Cancer Senior Fellowship



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 (ΔR1) changes in proportion to the concentration of molecular oxygen dissolved in plasma or interstitial tissue fluid. Therefore, well-oxygenated tissues show positive ΔR1. We hypothesized that the fraction of tumor tissue refractory to oxygen challenge (lack of positive ΔR1, 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 pO2 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, Oxy-R 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. Cancer Res; 76(4); 787–95. ©2015 AACR.

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