Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.
McLean, Mary A
Warren, Anne Y
Gill, Andrew B
Locke, Matthew J
Mills, Ian G
Robb, Fraser JL
Schulte, Rolf F
Gnanapragasam, Vincent J
Springer Science and Business Media LLC
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Sushentsev, N., McLean, M. A., Warren, A. Y., Benjamin, A. J., Brodie, C., Frary, A., Gill, A. B., et al. (2022). Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.. Nat Commun, 13 (1) https://doi.org/10.1038/s41467-022-28069-2
Funder: Gates Cambridge Trust; doi: https://doi.org/10.13039/501100005370
Funder: Prostate Cancer UK; doi: https://doi.org/10.13039/501100000771
Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289
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.
Article, /631/67/2321, /631/67/2327, /631/67/589/466, /692/4025/1752, /59/57, /82/51, /38/32, article
Prostate Cancer UK (PCUK; Grant PA14-012) and Cancer Research UK (CRUK; Grants C19212/A27150, C19212/A16628).
Prostate Cancer UK (PA14-012)
External DOI: https://doi.org/10.1038/s41467-022-28069-2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334770