Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.
- 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.
- Authors:
- N Sushentsev, MA McLean, AY Warren, AJV Benjamin, C Brodie, A Frary, AB Gill, J Jones, JD Kaggie, BW Lamb, MJ Locke, JL Miller, IG Mills, AN Priest, FJL Robb, N Shah, RF Schulte, MJ Graves, VJ Gnanapragasam, KM Brindle, T Barrett, FA Gallagher
- Journal:
- Nat Commun
- Citation info:
- 13(1):466
- Publication date:
- 24th Jan 2022
- Full text
- DOI