Spatial metabolomics informs the use of clinical imaging for improved detection of cribriform prostate cancer

Proc Natl Acad Sci U S A. 2025 Jul;122(26):e2502423122. doi: 10.1073/pnas.2502423122. Epub 2025 Jun 23.

Abstract

Cribriform prostate cancer (crPCa) is associated with poor clinical outcomes, yet its accurate detection remains challenging due to the poor sensitivity of standard-of-care diagnostic tools. Here, we use untargeted spatial metabolomics to identify fatty acid biosynthesis as a key metabolic pathway enriched in crPCa epithelium. We also show that imaging tumor lipid metabolism using [1-11C]acetate PET/CT and proton magnetic resonance spectroscopy differentiates cribriform from noncribriform intermediate-risk prostate cancers in two prospective patient cohorts. These findings support the feasibility of using clinical metabolic imaging techniques as adjunctive tools for improving crPCa detection in clinical practice, with prospective studies in larger cohorts warranted to obtain definitive results.

Keywords: MRI; cancer metabolism; nuclear medicine; prostate cancer; spectroscopy.

MeSH terms

  • Aged
  • Fatty Acids / biosynthesis
  • Humans
  • Lipid Metabolism
  • Male
  • Metabolomics* / methods
  • Middle Aged
  • Positron Emission Tomography Computed Tomography / methods
  • Prospective Studies
  • Prostatic Neoplasms* / diagnosis
  • Prostatic Neoplasms* / diagnostic imaging
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology

Substances

  • Fatty Acids