Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.
Authors
McLean, Mary A
Warren, Anne Y
Brodie, Cara
Gill, Andrew B
Locke, Matthew J
Mills, Ian G
Robb, Fraser JL
Shah, Nimish
Schulte, Rolf F
Gnanapragasam, Vincent J
Barrett, Tristan
Publication Date
2022-01-24Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
13
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
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
Description
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
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.
Keywords
Article, /631/67/2321, /631/67/2327, /631/67/589/466, /692/4025/1752, /59/57, /82/51, /38/32, article
Sponsorship
Prostate Cancer UK (PCUK; Grant PA14-012) and Cancer Research UK (CRUK; Grants C19212/A27150, C19212/A16628).
Funder references
Prostate Cancer UK (PA14-012)
Identifiers
s41467-022-28069-2, 28069
External DOI: https://doi.org/10.1038/s41467-022-28069-2
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334770
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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