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

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

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Abstract

Hyperpolarised 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.

Original languageEnglish
Article number466
JournalNature Communications
Volume13
DOIs
Publication statusPublished - 24 Jan 2022

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© 2022. The Author(s).

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