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.
Nature communications. 2024 Jul 16*** epublish ***
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, Ferdia A Gallagher
Department of Radiology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. ., Integrated BioAnalysis, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, UK., Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK., Predictive AI & Data, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, UK., Department of Radiology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK., Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK., Department of Urology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Department of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Bioscience, Early Oncology, AstraZeneca, Cambridge, UK.