Oxygen enhanced MRI accurately identifies, quantifies, and maps hypoxia in preclinical cancer models.
Authors
O'Connor, James P BBoult, J
Jamin, Y
Babur, M
Finegan, K
Williams, K
Little, R
Jackson, A
Parker, G
Reynolds, A
Waterton, J
Robinson, S
Affiliation
Institute of Cancer Sciences, University of ManchesterIssue Date
2015-12-09
Metadata
Show full item recordAbstract
There is a clinical need for non-invasive 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 (∆R1) changes in proportion to the concentration of molecular oxygen dissolved in plasma or interstitial tissue fluid. Therefore, well-oxygenated tissues show positive ∆R1. We hypothesized that the fraction of tumor tissue refractory to oxygen challenge (lack of positive ∆R1, 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 non-invasively and is immediately translatable to the clinic.Citation
Oxygen enhanced MRI accurately identifies, quantifies, and maps hypoxia in preclinical cancer models. 2015: Cancer ResJournal
Cancer ResearchDOI
10.1158/0008-5472.CAN-15-2062PubMed ID
26659574Type
ArticleLanguage
enISSN
1538-7445ae974a485f413a2113503eed53cd6c53
10.1158/0008-5472.CAN-15-2062
Scopus Count
Collections
Related articles
- Oxygen-enhanced MRI Is Feasible, Repeatable, and Detects Radiotherapy-induced Change in Hypoxia in Xenograft Models and in Patients with Non-small Cell Lung Cancer.
- Authors: Salem A, Little RA, Latif A, Featherstone AK, Babur M, Peset I, Cheung S, Watson Y, Tessyman V, Mistry H, Ashton G, Behan C, Matthews JC, Asselin MC, Bristow RG, Jackson A, Parker GJM, Faivre-Finn C, Williams KJ, O'Connor JPB
- Issue date: 2019 Jul 1
- Mapping Hypoxia in Renal Carcinoma with Oxygen-enhanced MRI: Comparison with Intrinsic Susceptibility MRI and Pathology.
- Authors: Little RA, Jamin Y, Boult JKR, Naish JH, Watson Y, Cheung S, Holliday KF, Lu H, McHugh DJ, Irlam J, West CML, Betts GN, Ashton G, Reynolds AR, Maddineni S, Clarke NW, Parker GJM, Waterton JC, Robinson SP, O'Connor JPB
- Issue date: 2018 Sep
- Combined Oxygen-Enhanced MRI and Perfusion Imaging Detect Hypoxia Modification from Banoxantrone and Atovaquone and Track Their Differential Mechanisms of Action.
- Authors: O'Connor JPB, Tessyman V, Little RA, Babur M, Forster D, Latif A, Cheung S, Lipowska-Bhalla G, Higgins GS, Asselin MC, Parker GJM, Williams KJ
- Issue date: 2024 Oct 1
- Noninvasive tumor hypoxia measurement using magnetic resonance imaging in murine U87 glioma xenografts and in patients with glioblastoma.
- Authors: Linnik IV, Scott ML, Holliday KF, Woodhouse N, Waterton JC, O'Connor JP, Barjat H, Liess C, Ulloa J, Young H, Dive C, Hodgkinson CL, Ward T, Roberts D, Mills SJ, Thompson G, Buonaccorsi GA, Cheung S, Jackson A, Naish JH, Parker GJ
- Issue date: 2014 May
- First-in-human technique translation of oxygen-enhanced MRI to an MR Linac system in patients with head and neck cancer.
- Authors: Dubec MJ, Buckley DL, Berks M, Clough A, Gaffney J, Datta A, McHugh DJ, Porta N, Little RA, Cheung S, Hague C, Eccles CL, Hoskin PJ, Bristow RG, Matthews JC, van Herk M, Choudhury A, Parker GJM, McPartlin A, O'Connor JPB
- Issue date: 2023 Jun