title: Detection of transgene expression using hyperpolarized 13C urea and diffusion-weighted magnetic resonance spectroscopy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK; Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: P Stephen
authors.initials: PS
authors.lastname: Patrick
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Kettunen
authors.forename: Sui-Seng
authors.initials: SS
authors.lastname: Tee
authors.forename: Tiago B
authors.initials: TB
authors.lastname: Rodrigues
authors.forename: Eva
authors.initials: E
authors.lastname: Serrao
authors.forename: Kerstin N
authors.initials: KN
authors.lastname: Timm
authors.forename: Sarah
authors.initials: S
authors.lastname: McGuire
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
mesh_terms: D000818:Animals; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D057809:HEK293 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D019076:Transgenes / Q000235:genetics; D014508:Urea / Q000493:pharmacokinetics*; D000096982:Urea Transporters
chemical_list: D002247:Carbon Isotopes; D026901:Membrane Transport Proteins; D014508:Urea; D000096982:Urea Transporters
keywords: 13C MRS; gene reporter; hyperpolarization; urea transporter