Metabolic imaging across scales reveals distinct prostate cancer phenotypes.

Autor: Sushentsev N; Department of Radiology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. ns784@medschl.cam.ac.uk., Hamm G; Integrated BioAnalysis, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, UK., Flint L; Integrated BioAnalysis, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, UK., Birtles D; Integrated BioAnalysis, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, UK., Zakirov A; Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK., Richings J; Predictive AI & Data, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, UK., Ling S; Integrated BioAnalysis, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, UK., Tan JY; Predictive AI & Data, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, UK., McLean MA; 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., Ayyappan V; Department of Radiology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Horvat Menih I; Department of Radiology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Brodie C; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK., Miller JL; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK., Mills IG; Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK., Gnanapragasam VJ; Department of Urology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Division of Urology, Department of Surgery, University of Cambridge, Cambridge, UK.; Cambridge Urology Translational Research and Clinical Trials Office, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge, UK., Warren AY; Department of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Barry ST; Bioscience, Early Oncology, AstraZeneca, Cambridge, UK., Goodwin RJA; Integrated BioAnalysis, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, UK., Barrett T; Department of Radiology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Gallagher FA; Department of Radiology, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 16; Vol. 15 (1), pp. 5980. Date of Electronic Publication: 2024 Jul 16.
DOI: 10.1038/s41467-024-50362-5
Abstrakt: Hyperpolarised magnetic resonance imaging (HP- 13 C-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- 13 C]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- 13 C]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- 13 C]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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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