Hyperpolarized MRI of Human Prostate Cancer Reveals Increased Lactate with Tumor Grade Driven by Monocarboxylate Transporter 1

Cell Metab. 2020 Jan 7;31(1):105-114.e3. doi: 10.1016/j.cmet.2019.08.024. Epub 2019 Sep 26.

Abstract

Metabolic imaging using hyperpolarized magnetic resonance can increase the sensitivity of MRI, though its ability to inform on relevant changes to biochemistry in humans remains unclear. In this work, we image pyruvate metabolism in patients, assessing the reproducibility of delivery and conversion in the setting of primary prostate cancer. We show that the time to max of pyruvate does not vary significantly within patients undergoing two separate injections or across patients. Furthermore, we show that lactate increases with Gleason grade. RNA sequencing data demonstrate a significant increase in the predominant pyruvate uptake transporter, monocarboxylate transporter 1. Increased protein expression was also observed in regions of high lactate signal, implicating it as the driver of lactate signal in vivo. Targeted DNA sequencing for actionable mutations revealed the highest lactate occurred in patients with PTEN loss. This work identifies a potential link between actionable genomic alterations and metabolic information derived from hyperpolarized pyruvate MRI.

Trial registration: ClinicalTrials.gov NCT02421380.

Keywords: glycolytic flux; hyperpolarized pyruvate; in vivo kinetics; metabolic imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carbon Isotopes / metabolism
  • Humans
  • Kinetics
  • Lactic Acid / metabolism*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / metabolism*
  • Neoplasm Grading
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / metabolism*
  • Pyruvic Acid / metabolism*
  • RNA-Seq
  • Reproducibility of Results
  • Symporters / genetics
  • Symporters / metabolism*

Substances

  • Carbon Isotopes
  • Monocarboxylic Acid Transporters
  • Symporters
  • monocarboxylate transport protein 1
  • Lactic Acid
  • Pyruvic Acid
  • PTEN Phosphohydrolase
  • PTEN protein, human

Associated data

  • ClinicalTrials.gov/NCT02421380