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dc.contributor.authorWoitek, Ramona
dc.contributor.authorMcLean, Mary
dc.contributor.authorUrsprung, Stephan
dc.contributor.authorRueda Palacio, Oscar
dc.contributor.authorManzano Garcia, Raquel
dc.contributor.authorLocke, Matthew J
dc.contributor.authorBeer, Lucian
dc.contributor.authorBaxter, Gabrielle
dc.contributor.authorRundo, Leonardo
dc.contributor.authorProvenzano, Elena
dc.contributor.authorKaggie, Joshua
dc.contributor.authorPatterson, Andrew
dc.contributor.authorFrary, Amy
dc.contributor.authorField-Rayner, Johanna
dc.contributor.authorPapalouka, Vasiliki
dc.contributor.authorKane, Justine
dc.contributor.authorBenjamin, Arnold JV
dc.contributor.authorGill, Andrew
dc.contributor.authorPriest, Andrew N
dc.contributor.authorLewis, David Y
dc.contributor.authorRussell, Roslin
dc.contributor.authorGrimmer, Ashley
dc.contributor.authorWhite, Brian
dc.contributor.authorLatimer-Bowman, Beth
dc.contributor.authorPatterson, Ilse
dc.contributor.authorSchiller, Amy
dc.contributor.authorCarmo, Bruno
dc.contributor.authorSlough, Rhys
dc.contributor.authorLanz, Titus
dc.contributor.authorWason, James
dc.contributor.authorSchulte, Rolf F
dc.contributor.authorChin, Suet-Feung
dc.contributor.authorGraves, Martin
dc.contributor.authorGilbert, Fiona
dc.contributor.authorAbraham, Jean E
dc.contributor.authorCaldas, Carlos
dc.contributor.authorBrindle, Kevin
dc.contributor.authorSala, Evis
dc.contributor.authorGallagher, Ferdia
dc.date.accessioned2021-10-06T23:30:06Z
dc.date.available2021-10-06T23:30:06Z
dc.date.issued2021-12-01
dc.identifier.issn0008-5472
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329055
dc.description.abstractHyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1-13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7-11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5-6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential. SIGNIFICANCE: Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7-11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.
dc.description.sponsorshipThis work was supported by the Mark Foundation for Cancer Research and Cancer Research UK Cambridge Centre (Grant C9685/A25177), Cancer Research UK (CRUK; Grants C8742/A18097, C19212/A16628, C19212/A911376, and C197/A16465), the Austrian Science Fund (Grant J4025-B26), the CRUK Cambridge Centre, the CRUK & Engineering and Physical Sciences Research Council Cancer Imaging Centre in Cambridge and Manchester, Addenbrooke’s Charitable Trust, and the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). The NIHR Cambridge Biomedical Research Centre (BRC) is a partnership between Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, funded by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. We also acknowledge funding from the UKRI Medical Research Council (MC UU 00002/16), the Cambridge Experimental Cancer Medicine Centre, a Wellcome Trust Strategic Award (095962), and Cambridge University Hospitals National Health Service Foundation Trust. We acknowledge the support of the Cambridge Breast Cancer Research Unit Laboratory in the collection of clinical data and samples and the Cancer Molecular Diagnostics for the extraction of DNA/RNA. The PARTNER Trial (https://clinicaltrials.gov/ct2/show/NCT03150576) was supported by Cancer Research UK and AstraZeneca (CRUK/14/048 and ESR-14-10241). The Personalised Breast Cancer Program is a collaboration between CRUK Cambridge Centre and Illumina (C507/A27657). We also acknowledge and are grateful for the involvement of our patients in these research projects.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherAmerican Association for Cancer Research (AACR)
dc.rightsAll rights reserved
dc.titleHyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients.
dc.typeArticle
prism.publicationDate2021
prism.publicationNameCancer Res
dc.identifier.doi10.17863/CAM.76500
dcterms.dateAccepted2021-10-06
rioxxterms.versionofrecord10.1158/0008-5472.CAN-21-1499
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-10-08
dc.contributor.orcidWoitek, Ramona [0000-0002-9146-9159]
dc.contributor.orcidMcLean, Mary [0000-0002-3752-0179]
dc.contributor.orcidUrsprung, Stephan [0000-0003-2476-178X]
dc.contributor.orcidRueda Palacio, Oscar [0000-0003-0008-4884]
dc.contributor.orcidBeer, Lucian [0000-0003-4388-7580]
dc.contributor.orcidBaxter, Gabrielle [0000-0002-8242-1559]
dc.contributor.orcidRundo, Leonardo [0000-0003-3341-5483]
dc.contributor.orcidKaggie, Joshua [0000-0001-6706-3442]
dc.contributor.orcidFrary, Amy [0000-0002-4373-3517]
dc.contributor.orcidBenjamin, Arnold JV [0000-0003-2063-8258]
dc.contributor.orcidGill, Andrew [0000-0002-9287-9563]
dc.contributor.orcidPriest, Andrew N [0000-0002-9771-4290]
dc.contributor.orcidLewis, David Y [0000-0001-9329-1326]
dc.contributor.orcidGrimmer, Ashley [0000-0001-6013-5271]
dc.contributor.orcidWason, James [0000-0002-4691-126X]
dc.contributor.orcidGraves, Martin [0000-0003-4327-3052]
dc.contributor.orcidGilbert, Fiona [0000-0002-0124-9962]
dc.contributor.orcidCaldas, Carlos [0000-0003-3547-1489]
dc.contributor.orcidBrindle, Kevin [0000-0003-3883-6287]
dc.contributor.orcidSala, Evis [0000-0002-5518-9360]
dc.contributor.orcidGallagher, Ferdia [0000-0003-4784-5230]
dc.identifier.eissn1538-7445
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMark Foundation for Cancer Research US Ltd (Unknown)
pubs.funder-project-idWellcome Trust (095962/Z/11/Z)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research UK (C12912/A27150)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (3819-1819-07)
pubs.funder-project-idCancer Research UK (C19212/A29082)
pubs.funder-project-idCancer Research UK (CB4100)
pubs.funder-project-idCancer Research UK (C14303/A17197)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (C96/A25177)
pubs.funder-project-idCancer Research UK (A27657)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (60098573)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (CB4140)
pubs.funder-project-idCancer Research UK (CRUK-A3086)
pubs.funder-project-idCancer Research UK (CRUK-A9401)
pubs.funder-project-idCancer Research UK (CRUK-A16942)
pubs.funder-project-idCancer Research UK (CRUK-A7325)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCancer Research UK (unknown)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (RG51913)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (unknown)
pubs.funder-project-idMedical Research Council (MR/M009041/1)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0515-10090)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (Unknown)
pubs.funder-project-idCancer Research UK (CRUK-A7199)
pubs.funder-project-idCancer Research UK (CRUK-A15580)
pubs.funder-project-idCancer Research UK (C507/A16278)
pubs.funder-project-idEngineering and Physical Sciences Research Council (NS/A000023/1)
cam.issuedOnline2021-10-08
cam.orpheus.successMon Oct 11 07:30:24 BST 2021 - Embargo updated
rioxxterms.freetoread.startdate2022-10-08


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