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    Oxygen enhanced MRI accurately identifies, quantifies, and maps hypoxia in preclinical cancer models.

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    Authors
    O'Connor, James P B
    Boult, J
    Jamin, Y
    Babur, M
    Finegan, K
    Williams, K
    Little, R
    Jackson, A
    Parker, G
    Reynolds, A
    Waterton, J
    Robinson, S
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    Affiliation
    Institute of Cancer Sciences, University of Manchester
    Issue Date
    2015-12-09
    
    Metadata
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    Abstract
    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 Res
    Journal
    Cancer Research
    URI
    http://hdl.handle.net/10541/593305
    DOI
    10.1158/0008-5472.CAN-15-2062
    PubMed ID
    26659574
    Type
    Article
    Language
    en
    ISSN
    1538-7445
    ae974a485f413a2113503eed53cd6c53
    10.1158/0008-5472.CAN-15-2062
    Scopus Count
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    All Paterson Institute for Cancer Research

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