title: Spin echo measurements of the extravasation and tumor cell uptake of hyperpolarized [1-(13) C]lactate and [1-(13) C]pyruvate.
abstract: OBJECTIVE
  To assess the blood-tissue distribution of hyperpolarized (13) C-labeled molecules in vivo.
  
  
  METHODS
  Spin-echo experiments with simultaneous acquisition of the free induction decay (FID) signal following the excitation pulse and the spin-echo signal, were used to monitor hyperpolarized [1-(13) C]lactate, [1-(13) C]pyruvate, and the perfusion marker, [(13) C]HP001, following their intravenous injection into tumor-bearing mice. Apparent T2 relaxation times and diffusion coefficients were also measured.
  
  
  RESULTS
  An increasing tumor echo/FID ratio was observed for all three molecules, which could be explained by their extravasation into the tumor interstitial space, where T2 relaxation times were longer and diffusion coefficients smaller. Inhibition of the monocarboxylate transporter, which decreased by 40% the label exchange between pyruvate and lactate, reduced the increase in the echo/FID ratio for pyruvate and lactate, but not for HP001, demonstrating that some of the increase in the echo/FID ratio was due to cell uptake of lactate and pyruvate. The different relaxation and diffusion behavior of the intravascular and extravascular signals affected measurements of the apparent label exchange rate constants.
  
  
  CONCLUSIONS
  Simultaneous collection of both FID and echo signals can provide information on cell uptake thus giving further insight into the kinetics of hyperpolarized (13) C label exchange. Care is needed when comparing exchange rate constants determined in spin-echo-based studies.
authors.affiliation: Cancer Research UK Cambridge Research Institute, Cambridge, UK; Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Kettunen
authors.forename: Brett W C
authors.initials: BW
authors.lastname: Kennedy
authors.forename: De-En
authors.initials: DE
authors.lastname: Hu
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brindle
mesh_terms: D000818:Animals; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D005260:Female; D019344:Lactic Acid / Q000493:pharmacokinetics*; D008223:Lymphoma / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013113:Spin Labels
chemical_list: D002247:Carbon Isotopes; D019275:Radiopharmaceuticals; D013113:Spin Labels; D019344:Lactic Acid
keywords: diffusion; monocarboxylate transporter; perfusion; relaxation; transport