Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediaterisk human prostate cancer
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; Priest, Andrew N.; Robb, Fraser J. L.; Shah, Nimish; Schulte, Rolf S.; Graves, Martin J.; Gnanapragasam, Vincent J.; Brindle, Kevin M.; Barrett, Tristan; Gallagher, Ferdia A.
Journal article, Peer reviewed
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Original versionNature Communications. 2022, 13, 466. 10.1038/s41467-022-28069-2
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.