title: Quantitative (31)P HR-MAS MR spectroscopy for detection of response to PI3K/mTOR inhibition in breast cancer xenografts.
abstract: OBJECTIVE
  Phospholipid metabolites are of importance in cancer studies, and have been suggested as candidate metabolic biomarkers for response to targeted anticancer drugs. The purpose of this study was to develop a phosphorus ((31) P) high resolution magic angle spinning magnetic resonance spectroscopy protocol for quantification of phosphorylated metabolites in intact cancer tissue.
  
  
  METHODS
  (31) P spectra were acquired on a 14.1 T spectrometer with a triplet (1) H/(13) C/(31) P MAS probe. Quantification of metabolites was performed using the PULCON principle. Basal-like and luminal-like breast cancer xenografts were treated with the dual PI3K/mTOR inhibitor BEZ235, and the impact of treatment on the concentration of phosphocholine, glycerophosphocholine, phosphoethanolamine and glycerophosphoethanolamine was evaluated.
  
  
  RESULTS
  In basal-like xenografts, BEZ235 treatment induced a significant decrease in phosphoethanolamine (-25.6%, P = 0.01) whilst phosphocholine (16.5%, P = 0.02) and glycerophosphocholine (37.3%, P < 0.001) were significantly increased. The metabolic changes could partially be explained by increased levels of phospholipase A2 group 4A (PLA2G4A).
  
  
  CONCLUSIONS
  (31) P high resolution magic angle spinning magnetic resonance spectroscopy is a useful method for quantitative assessment of metabolic responses to PI3K inhibition. Using the PULCON principle for quantification, the levels of phosphocholine, glycerophosphocholine, phosphoethanolamine, and glycerophosphoethanolamine could be evaluated with high precision and accuracy.
authors.affiliation: Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Morteza
authors.initials: M
authors.lastname: Esmaeili
authors.forename: Tone F
authors.initials: TF
authors.lastname: Bathen
authors.forename: Olav
authors.initials: O
authors.lastname: Engebråten
authors.forename: Gunhild M
authors.initials: GM
authors.lastname: Mælandsmo
authors.forename: Ingrid S
authors.initials: IS
authors.lastname: Gribbestad
authors.forename: Siver A
authors.initials: SA
authors.lastname: Moestue
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D004983:Ethanolamines / Q000378:metabolism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010759:Phosphorus Isotopes; D010767:Phosphorylcholine / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004983:Ethanolamines; D007093:Imidazoles; D010714:Phosphatidylethanolamines; D010759:Phosphorus Isotopes; D011804:Quinolines; D010767:Phosphorylcholine; C002449:glycerophosphoethanolamine; C005448:phosphorylethanolamine; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C531198:dactolisib
keywords: absolute quantification; choline metabolism; ethanolamine; glycerophosphocholine; phospholipase A2; phospholipid