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dc.contributor.authorO'Connor, JPB
dc.contributor.authorBoult, JKR
dc.contributor.authorJamin, Y
dc.contributor.authorBabur, M
dc.contributor.authorFinegan, KG
dc.contributor.authorWilliams, KJ
dc.contributor.authorLittle, RA
dc.contributor.authorJackson, A
dc.contributor.authorParker, GJM
dc.contributor.authorReynolds, AR
dc.contributor.authorWaterton, JC
dc.contributor.authorRobinson, SP
dc.date.accessioned2020-06-26T08:20:44Z
dc.date.issued2016-02
dc.identifier.citationCancer research, 2016, 76 (4), pp. 787 - 795
dc.identifier.issn0008-5472
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3773
dc.identifier.eissn1538-7445
dc.identifier.doi10.1158/0008-5472.can-15-2062
dc.description.abstractThere 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.
dc.formatPrint-Electronic
dc.format.extent787 - 795
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectOxygen
dc.subjectMagnetic Resonance Imaging
dc.subjectRadiography
dc.subjectPrognosis
dc.subjectCell Hypoxia
dc.titleOxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models.
dc.typeJournal Article
dcterms.dateAccepted2015-11-09
rioxxterms.versionofrecord10.1158/0008-5472.can-15-2062
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-02
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer research
pubs.issue4
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Tumour Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Quantitative Biomedical Imaging
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Tumour Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Quantitative Biomedical Imaging
pubs.publication-statusPublished
pubs.volume76
pubs.embargo.termsNot known
icr.researchteamTumour Biologyen_US
icr.researchteamPre-Clinical MRIen_US
icr.researchteamQuantitative Biomedical Imagingen_US
dc.contributor.icrauthorReynolds, Andrewen
dc.contributor.icrauthorBoult, Jessicaen
dc.contributor.icrauthorJamin, Yannen
dc.contributor.icrauthorRobinson, Simonen
dc.contributor.icrauthorO'Connor, James Patricken


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