Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models.
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Date
2015-11-19Author
O'Connor, JPB
Boult, JKR
Jamin, Y
Babur, M
Finegan, KG
Williams, KJ
Little, RA
Jackson, A
Parker, GJM
Reynolds, AR
Waterton, JC
Robinson, SP
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Humans
Neoplasms
Oxygen
Magnetic Resonance Imaging
Radiography
Prognosis
Cell Hypoxia
Research team
Tumour Biology
Pre-Clinical MRI
Quantitative Biomedical Imaging
Language
eng
Date accepted
2015-11-09
License start date
2016-02
Citation
Cancer research, 2016, 76 (4), pp. 787 - 795
Publisher
AMER ASSOC CANCER RESEARCH