In vivo ³¹P magnetic resonance spectroscopic imaging (MRSI) for metabolic profiling of human breast cancer xenografts

J Magn Reson Imaging. 2015 Mar;41(3):601-9. doi: 10.1002/jmri.24588. Epub 2014 Feb 14.

Abstract

Purpose: To study cancer associated with abnormal metabolism of phospholipids, of which several have been proposed as biomarkers for malignancy or to monitor response to anticancer therapy. We explored 3D (31) P magnetic resonance spectroscopic imaging (MRSI) at high magnetic field for in vivo assessment of individual phospholipids in two patient-derived breast cancer xenografts representing good and poor prognosis (luminal- and basal-like tumors).

Materials and methods: Metabolic profiles from luminal-like and basal-like xenograft tumors were obtained in vivo using 3D (31) P MRSI at 11.7T and from tissue extracts in vitro at 14.1T. Gene expression analysis was performed in order to support metabolic differences between the two xenografts.

Results: In vivo (31) P MR spectra were obtained in which the prominent resonances from phospholipid metabolites were detected at a high signal-to-noise ratio (SNR >7.5). Metabolic profiles obtained in vivo were in agreement with those obtained in vitro and could be used to discriminate between the two xenograft models, based on the levels of phosphocholine, phosphoethanolamine, glycerophosphocholine, and glycerophosphoethanolamine. The differences in phospholipid metabolite concentration could partly be explained by gene expression profiles.

Conclusion: Noninvasive metabolic profiling by 3D (31) P MRSI can discriminate between subtypes of breast cancer based on different concentrations of choline- and ethanolamine-containing phospholipids.

Keywords: basal-like; choline metabolism; ethanolamine kinase; high field; phospholipid; phosphorus MR spectroscopic imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / metabolism*
  • Choline / metabolism
  • Female
  • Heterografts / metabolism*
  • Humans
  • Imaging, Three-Dimensional
  • Magnetic Resonance Spectroscopy / methods*
  • Metabolome*
  • Mice
  • Mice, Inbred BALB C
  • Phosphorus Isotopes
  • Signal-To-Noise Ratio
  • Transplantation, Heterologous

Substances

  • Biomarkers, Tumor
  • Phosphorus Isotopes
  • Choline