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Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer

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cam.depositDate2021-12-06
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dc.contributor.authorSushentsev, Nikita
dc.contributor.authorMcLean, Mary A
dc.contributor.authorWarren, Anne
dc.contributor.authorBenjamin, Arnold JV
dc.contributor.authorBrodie, Cara
dc.contributor.authorFrary, Amy
dc.contributor.authorGill, Andrew
dc.contributor.authorJones, Julia
dc.contributor.authorKaggie, Joshua
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 S
dc.contributor.authorGraves, Martin J
dc.contributor.authorGnanapragasam, Vincent
dc.contributor.authorBrindle, Kevin
dc.contributor.authorBarrett, Tristan
dc.contributor.authorGallagher, Ferdia
dc.contributor.orcidWarren, Anne [0000-0002-1170-7867]
dc.contributor.orcidFrary, Amy [0000-0002-4373-3517]
dc.contributor.orcidGill, Andrew [0000-0002-9287-9563]
dc.contributor.orcidKaggie, Joshua [0000-0001-6706-3442]
dc.contributor.orcidGnanapragasam, Vincent [0000-0003-4722-4207]
dc.contributor.orcidBrindle, Kevin [0000-0003-3883-6287]
dc.contributor.orcidBarrett, Tristan [0000-0002-1180-1474]
dc.contributor.orcidGallagher, Ferdia [0000-0003-4784-5230]
dc.date.accessioned2021-12-08T00:30:16Z
dc.date.available2021-12-08T00:30:16Z
dc.date.updated2021-12-06T09:00:30Z
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.identifier.doi10.17863/CAM.78706
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331260
dc.language.isoeng
dc.publisherNature Research
dc.publisher.departmentDepartment of Radiology
dc.publisher.departmentDepartment of Biochemistry
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleHyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer
dc.typeArticle
dcterms.dateAccepted2021-12-02
prism.publicationNameNature Communications
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
pubs.licence-identifierapollo-deposit-licence-2-1
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR

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