Metabolic imaging across scales reveals distinct prostate cancer phenotypes

Nikita Sushentsev (), Gregory Hamm, Lucy Flint, Daniel Birtles, Aleksandr Zakirov, Jack Richings, Stephanie Ling, Jennifer Y. Tan, Mary A. McLean, Vinay Ayyappan, Ines Horvat Menih, Cara Brodie, Jodi L. Miller, Ian G. Mills, Vincent J. Gnanapragasam, Anne Y. Warren, Simon T. Barry, Richard J. A. Goodwin, Tristan Barrett and Ferdia A. Gallagher
Additional contact information
Nikita Sushentsev: University of Cambridge and Cambridge University Hospitals NHS Foundation Trust
Gregory Hamm: AstraZeneca
Lucy Flint: AstraZeneca
Daniel Birtles: AstraZeneca
Aleksandr Zakirov: University of Cambridge
Jack Richings: AstraZeneca
Stephanie Ling: AstraZeneca
Jennifer Y. Tan: AstraZeneca
Mary A. McLean: University of Cambridge and Cambridge University Hospitals NHS Foundation Trust
Vinay Ayyappan: University of Cambridge and Cambridge University Hospitals NHS Foundation Trust
Ines Horvat Menih: University of Cambridge and Cambridge University Hospitals NHS Foundation Trust
Cara Brodie: University of Cambridge
Jodi L. Miller: University of Cambridge
Ian G. Mills: Queen’s University Belfast
Vincent J. Gnanapragasam: Cambridge University Hospitals NHS Foundation Trust
Anne Y. Warren: Cambridge University Hospitals NHS Foundation Trust
Simon T. Barry: AstraZeneca
Richard J. A. Goodwin: AstraZeneca
Tristan Barrett: University of Cambridge and Cambridge University Hospitals NHS Foundation Trust
Ferdia A. Gallagher: University of Cambridge and Cambridge University Hospitals NHS Foundation Trust

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract Hyperpolarised magnetic resonance imaging (HP-13C-MRI) has shown promise as a clinical tool for detecting and characterising prostate cancer. Here we use a range of spatially resolved histological techniques to identify the biological mechanisms underpinning differential [1-13C]lactate labelling between benign and malignant prostate, as well as in tumours containing cribriform and non-cribriform Gleason pattern 4 disease. Here we show that elevated hyperpolarised [1-13C]lactate signal in prostate cancer compared to the benign prostate is primarily driven by increased tumour epithelial cell density and vascularity, rather than differences in epithelial lactate concentration between tumour and normal. We also demonstrate that some tumours of the cribriform subtype may lack [1-13C]lactate labelling, which is explained by lower epithelial lactate dehydrogenase expression, higher mitochondrial pyruvate carrier density, and increased lipid abundance compared to lactate-rich non-cribriform lesions. These findings highlight the potential of combining spatial metabolic imaging tools across scales to identify clinically significant metabolic phenotypes in prostate cancer.

Date: 2024
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DOI: 10.1038/s41467-024-50362-5

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