Cell Metabolism
Volume 31, Issue 1, 7 January 2020, Pages 105-114.e3
Journal home page for Cell Metabolism

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

https://doi.org/10.1016/j.cmet.2019.08.024Get rights and content
Under an Elsevier user license
open archive

Highlights

  • HP pyruvate can be safely infused multiple times and measures reproducible kinetics

  • Tumors with increased Gleason grades had increased levels of hyperpolarized lactate

  • Regions of high HP lactate correlated with elevated monocarboxylate transporter 1

  • Conversion of HP pyruvate to lactate was increased in tumors with loss of PTEN

Summary

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.

Keywords

metabolic imaging
glycolytic flux
in vivo kinetics
hyperpolarized pyruvate

Cited by (0)

11

These authors contributed equally

12

Present address: Department of Radiology, University of Maryland, Baltimore, MD, USA

13

Lead Contact