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dc.contributor.authorMair, Richard
dc.contributor.authorWright, Alan
dc.contributor.authorRos, Susana
dc.contributor.authorHu, De-En
dc.contributor.authorBooth, Tom
dc.contributor.authorKreis, Felix
dc.contributor.authorRao, Jyotsna
dc.contributor.authorWatts, Colin
dc.contributor.authorBrindle, Kevin
dc.date.accessioned2018-10-03T04:43:18Z
dc.date.available2018-10-03T04:43:18Z
dc.date.issued2018-09-15
dc.identifier.issn0008-5472
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283018
dc.description.abstract13C MRI of hyperpolarized [1-13C]pyruvate metabolism has been used in oncology to detect disease, investigate disease progression, and monitor response to treatment with a view to guiding treatment in individual patients. This technique has translated to the clinic with initial studies in prostate cancer. Here, we use the technique to investigate its potential uses in patients with glioblastoma (GB). We assessed the metabolism of hyperpolarized [1-13C]pyruvate in an orthotopically implanted cell line model (U87) of GB and in patient-derived tumors, where these were produced by orthotopic implantation of cells derived from different patients. Lactate labeling was higher in the U87 tumor when compared with patient-derived tumors, which displayed intertumoral heterogeneity, reflecting the intra- and intertumoral heterogeneity in the patients' tumors from which they were derived. Labeling in some patient-derived tumors could be observed before their appearance in morphologic images, whereas in other tumors it was not significantly greater than the surrounding brain. Increased lactate labeling in tumors correlated with c-Myc-driven expression of hexokinase 2, lactate dehydrogenase A, and the monocarboxylate transporters and was accompanied by increased radioresistance. Because c-Myc expression correlates with glioma grade, this study demonstrates that imaging with hyperpolarized [1-13C]pyruvate could be used clinically with patients with GB to determine disease prognosis, to detect early responses to drugs that modulate c-Myc expression, and to select tumors, and regions of tumors for increased radiotherapy dose.Significance: Metabolic imaging with hyperpolarized [1-13C]pyruvate detects low levels of c-Myc-driven glycolysis in patient-derived glioblastoma models, which, when translated to the clinic, could be used to detect occult disease, determine disease prognosis, and target radiotherapy. Cancer Res; 78(18); 5408-18. ©2018 AACR.
dc.description.sponsorshipThe work was supported by a Cancer Research UK Programme grant (17242) and by the CRUK-EPSRC Imaging Centre in Cambridge and Manchester (16465) awarded to K. M. Brindle. F. Kreis was supported by a Marie Curie ITN studentship (EUROPOL) and R. Mair by Addenbrooke's Charitable Trust and a CRUK Cambridge Centre Fellowship.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherAmerican Association for Cancer Research (AACR)
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectRats
dc.subjectRats, Nude
dc.subjectGlioblastoma
dc.subjectBrain Neoplasms
dc.subjectDisease Models, Animal
dc.subjectDoxycycline
dc.subjectProto-Oncogene Proteins c-myc
dc.subjectRNA, Small Interfering
dc.subjectMagnetic Resonance Imaging
dc.subjectPrognosis
dc.subjectMagnetic Resonance Spectroscopy
dc.subjectNeoplasm Transplantation
dc.subjectGlycolysis
dc.subjectFemale
dc.subjectMale
dc.subjectExome
dc.subjectHeterografts
dc.titleMetabolic Imaging Detects Low Levels of Glycolytic Activity That Vary with Levels of c-Myc Expression in Patient-Derived Xenograft Models of Glioblastoma.
dc.typeArticle
prism.endingPage5418
prism.issueIdentifier18
prism.publicationDate2018
prism.publicationNameCancer Res
prism.startingPage5408
prism.volume78
dc.identifier.doi10.17863/CAM.30382
dcterms.dateAccepted2018-07-23
rioxxterms.versionofrecord10.1158/0008-5472.CAN-18-0759
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-09
dc.contributor.orcidMair, Richard [0000-0001-8235-5689]
dc.contributor.orcidWright, Alan [0000-0002-4577-5681]
dc.contributor.orcidKreis, Felix [0000-0003-3340-3861]
dc.contributor.orcidBrindle, Kevin [0000-0003-3883-6287]
dc.identifier.eissn1538-7445
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research UK (CB4100)
pubs.funder-project-idAddenbrooke's Charitable Trust (ACT) (unknown)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (642773)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research UK (C48525/A18345)
pubs.funder-project-idMedical Research Council (G1000265)
cam.issuedOnline2018-07-27
datacite.issupplementedby.urlhttps://doi.org/10.17863/CAM.26052
rioxxterms.freetoread.startdate2019-09-30


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