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dc.contributor.authorSushentsev, Nikita
dc.contributor.authorMcLean, Mary A
dc.contributor.authorWarren, Anne Y
dc.contributor.authorBenjamin, Arnold JV
dc.contributor.authorBrodie, Cara
dc.contributor.authorFrary, Amy
dc.contributor.authorGill, Andrew B
dc.contributor.authorJones, Julia
dc.contributor.authorKaggie, Joshua D
dc.contributor.authorLamb, Benjamin W
dc.contributor.authorLocke, Matthew J
dc.contributor.authorMiller, Jodi L
dc.contributor.authorMills, Ian G
dc.contributor.authorPriest, Andrew N
dc.contributor.authorRobb, Fraser JL
dc.contributor.authorShah, Nimish
dc.contributor.authorSchulte, Rolf F
dc.contributor.authorGraves, Martin J
dc.contributor.authorGnanapragasam, Vincent J
dc.contributor.authorBrindle, Kevin M
dc.contributor.authorBarrett, Tristan
dc.contributor.authorGallagher, Ferdia A
dc.date.accessioned2022-03-08T16:14:51Z
dc.date.available2022-03-08T16:14:51Z
dc.date.issued2022-01-24
dc.date.submitted2021-07-02
dc.identifier.issn2041-1723
dc.identifier.others41467-022-28069-2
dc.identifier.other28069
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334770
dc.descriptionFunder: Gates Cambridge Trust; doi: https://doi.org/10.13039/501100005370
dc.descriptionFunder: Prostate Cancer UK; doi: https://doi.org/10.13039/501100000771
dc.descriptionFunder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289
dc.description.abstractHyperpolarised magnetic resonance imaging (HP 13C-MRI) is an emerging clinical technique to detect [1-13C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-13C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-13C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP 13C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-13C]lactate labelling correlated with epithelial mRNA expression of the enzyme lactate dehydrogenase (LDHA and LDHB combined), and the ratio of lactate transporter expression between the epithelial and stromal compartments (epithelium-to-stroma MCT4). We observe similar changes in MCT4, LDHA, and LDHB between tumours with primary Gleason patterns 3 and 4 in an independent TCGA cohort. Therefore, HP 13C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments.
dc.description.sponsorshipProstate Cancer UK (PCUK; Grant PA14-012) and Cancer Research UK (CRUK; Grants C19212/A27150, C19212/A16628).
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/67/2321
dc.subject/631/67/2327
dc.subject/631/67/589/466
dc.subject/692/4025/1752
dc.subject/59/57
dc.subject/82/51
dc.subject/38/32
dc.subjectarticle
dc.titleHyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.
dc.typeArticle
dc.date.updated2022-03-08T16:14:50Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
dc.identifier.doi10.17863/CAM.82200
dcterms.dateAccepted2021-12-02
rioxxterms.versionofrecord10.1038/s41467-022-28069-2
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidSushentsev, Nikita [0000-0003-4500-9714]
dc.contributor.orcidBenjamin, Arnold JV [0000-0003-2063-8258]
dc.contributor.orcidFrary, Amy [0000-0002-4373-3517]
dc.contributor.orcidJones, Julia [0000-0001-9819-8091]
dc.contributor.orcidKaggie, Joshua D [0000-0001-6706-3442]
dc.contributor.orcidLamb, Benjamin W [0000-0003-2220-893X]
dc.contributor.orcidMiller, Jodi L [0000-0001-6870-204X]
dc.contributor.orcidPriest, Andrew N [0000-0002-9771-4290]
dc.contributor.orcidGraves, Martin J [0000-0003-4327-3052]
dc.contributor.orcidBrindle, Kevin M [0000-0003-3883-6287]
dc.contributor.orcidGallagher, Ferdia A [0000-0003-4784-5230]
dc.identifier.eissn2041-1723
pubs.funder-project-idProstate Cancer UK (PA14-012)
cam.issuedOnline2022-01-24


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