Detection of transgene expression using hyperpolarized 13C urea and diffusion-weighted magnetic resonance spectroscopy

Magn Reson Med. 2015 Apr;73(4):1401-6. doi: 10.1002/mrm.25254. Epub 2014 Apr 14.

Abstract

Purpose: To assess the potential of a gene reporter system, based on a urea transporter (UTB) and hyperpolarized [(13) C]urea.

Methods: Mice were implanted subcutaneously with either unmodified control cells or otherwise identical cells expressing UTB. After injection of hyperpolarized [(13) C]urea, a spin echo sequence was used to measure urea concentration, T1 , and diffusion in control and UTB-expressing tissue.

Results: The apparent diffusion coefficient of hyperpolarized urea was 21% lower in tissue expressing UTB, in comparison with control tissue (P < 0.05, 1-tailed t-test, n = 6 in each group). No difference in water apparent diffusion coefficient or cellularity between these tissues was found, indicating that they were otherwise similar in composition.

Conclusion: Expression of UTB, by mediating cell uptake of urea, lowers the apparent diffusion coefficient of hyperpolarized (13) C urea in tissue and thus the transporter has the potential to be used as a magnetic resonance-based gene reporter in vivo. Magn Reson Med 73:1401-1406, 2015. © 2014 Wiley Periodicals, Inc.

Keywords: 13C MRS; gene reporter; hyperpolarization; urea transporter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Isotopes / pharmacokinetics
  • HEK293 Cells
  • Humans
  • Magnetic Resonance Spectroscopy / methods*
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Mice, SCID
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Distribution
  • Transgenes / genetics
  • Urea / pharmacokinetics*
  • Urea Transporters

Substances

  • Carbon Isotopes
  • Membrane Transport Proteins
  • Urea