title: Intracerebral synthesis of glutamine from hyperpolarized glutamate.
abstract: Changes in glutamate (Glu) levels occur in a number of neurodegenerative diseases. We proposed the use of13C spectroscopy and the highly amplified signal generated by hyperpolarization to achieve spatial and temporal resolutions adequate for in vivo studies of Glu metabolism in the healthy rat brain. Thus, we investigated uptake of hyperpolarized [1-13C]Glu after a temporary blood-brain barrier (BBB) disruption protocol and its conversion to glutamine (Gln) in the brain.
  
  
  
  [1-13C]Glu was hyperpolarized using the dynamic nuclear polarization process. A temporary BBB disruption using mannitol allowed hyperpolarized [1-13C]Glu to reach the brain. Then, hyperpolarized [1-13C]Glu brain metabolism was observed in vivo by MR spectroscopy experiments at 3T. Products synthesized from [1-13C]Glu were assigned via liquid chromatography-mass spectrometry.
  
  
  
  Hyperpolarized [1-13C]Glu reached 20% ± 2.3% polarization after 90 min. After validation of the BBB disruption protocol, hyperpolarized [1-13C]Glu (175.4 ppm) was detected inside the rat brain, and the formation of [1-13C]Gln at 174.9 ppm was also observed.
  
  
  
  The Gln synthesis from hyperpolarized [1-13C]Glu can be monitored in vivo in the healthy rat brain after opening the BBB. Magn Reson Med 78:1296-1305, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
authors.affiliation: Auvergne University, UFR Medicine, EA7280, Clermont-Ferrand, France.|Centre de Résonance Magnétique des Systèmes Biologiques, UMR 5536, Victor Segalen University, CNRS, Bordeaux, France.
authors.forename: Leslie
authors.initials: L
authors.lastname: Mazuel
authors.affiliation: GE Global Research, Munich, Germany.
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Schulte
authors.affiliation: CHU Gabriel Montpied, MRI Department, Clermont-Ferrand, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cladière
authors.affiliation: CHU Gabriel Montpied, MRI Department, Clermont-Ferrand, France.
authors.forename: Claudine
authors.initials: C
authors.lastname: Spéziale
authors.affiliation: Plateforme d'Exploration du Métabolisme, Institut de Chimie de Clermont-Ferrand, Aubière, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Lagrée
authors.affiliation: Mass Spectrometry Department, Institut de Chimie de Clermont-Ferrand, Aubière, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Leremboure
authors.affiliation: CHU Gabriel Montpied, MRI Department, Clermont-Ferrand, France.
authors.forename: Betty
authors.initials: B
authors.lastname: Jean
authors.affiliation: Auvergne University, UFR Medicine, EA7280, Clermont-Ferrand, France.|CHU Gabriel Montpied, Neurology Department, Clermont-Ferrand, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Durif
authors.affiliation: CHU Gabriel Montpied, MRI Department, Clermont-Ferrand, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Chassain
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002247:Carbon Isotopes / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D005973:Glutamine / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002247:Carbon Isotopes; D005973:Glutamine; D018698:Glutamic Acid; D005947:Glucose
keywords: 13C MR spectroscopy; blood-brain barrier disruption; dynamic nuclear polarization; glutamate metabolism; hyperpolarized [1-13C]glutamate