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

Nature Communications, ISSN: 2041-1723, Vol: 13, Issue: 1, Page: 466
2022
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Article Description

Hyperpolarised magnetic resonance imaging (HP C-MRI) is an emerging clinical technique to detect [1-C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised [1-C]pyruvate. Here we differentiate clinically significant PCa from indolent disease in a low/intermediate-risk population by correlating [1-C]lactate labelling on MRI with the percentage of Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, we show that HP C-MRI predominantly measures metabolism in the epithelial compartment of the tumour, rather than the stroma. MRI-derived tumour [1-C]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 C-MRI can metabolically phenotype clinically significant disease based on underlying metabolic differences in the epithelial and stromal tumour compartments.

Bibliographic Details

Sushentsev, Nikita; McLean, Mary A; Warren, Anne Y; Benjamin, Arnold J V; Brodie, Cara; Frary, Amy; Gill, Andrew B; Jones, Julia; Kaggie, Joshua D; Lamb, Benjamin W; Locke, Matthew J; Miller, Jodi L; Mills, Ian G; Priest, Andrew N; Robb, Fraser J L; Shah, Nimish; Schulte, Rolf F; Graves, Martin J; Gnanapragasam, Vincent J; Brindle, Kevin M; Barrett, Tristan; Gallagher, Ferdia A

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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