Hyperpolarised 13C-MRI identifies the emergence of a glycolytic cell population within intermediate-risk human prostate cancer.


Change log
Authors
McLean, Mary A 
Warren, Anne Y 
Benjamin, Arnold JV  ORCID logo  https://orcid.org/0000-0003-2063-8258
Brodie, Cara 
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.

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

Keywords
Aged, Aged, 80 and over, Cohort Studies, Epithelial Cells, Glycolysis, Humans, L-Lactate Dehydrogenase, Magnetic Resonance Imaging, Male, Middle Aged, Monocarboxylic Acid Transporters, Muscle Proteins, Prospective Studies, Prostatic Neoplasms, Pyruvic Acid, Stromal Cells
Journal Title
Nat Commun
Conference Name
Journal ISSN
2041-1723
2041-1723
Volume Title
13
Publisher
Springer Science and Business Media LLC
Sponsorship
Prostate Cancer UK (PA14-012)
Prostate Cancer UK (PCUK; Grant PA14-012) and Cancer Research UK (CRUK; Grants C19212/A27150, C19212/A16628).