title: Imaging cerebral 2-ketoisocaproate metabolism with hyperpolarized (13)C magnetic resonance spectroscopic imaging.
abstract: The branched chain amino acid transaminase (BCAT) has an important role in nitrogen shuttling and glutamate metabolism in the brain. The purpose of this study was to describe the cerebral distribution and metabolism of hyperpolarized 2-keto[1-(13)C]isocaproate (KIC) in the normal rat using magnetic resonance modalities. Hyperpolarized KIC is metabolized to [1-(13)C]leucine (leucine) by BCAT. The results show that KIC and its metabolic product, leucine, are present at imageable quantities 20 seconds after end of KIC administration throughout the brain. Further, significantly higher metabolism was observed in hippocampal regions compared with the muscle tissue. In conclusion, the cerebral metabolism of hyperpolarized KIC is imaged and hyperpolarized KIC may be a promising substrate for evaluation of cerebral BCAT activity in conjunction with neurodegenerative disease.
authors.affiliation: Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Sadia A
authors.initials: SA
authors.lastname: Butt
authors.forename: Lise V
authors.initials: LV
authors.lastname: Søgaard
authors.forename: Peter O
authors.initials: PO
authors.lastname: Magnusson
authors.forename: Mette H
authors.initials: MH
authors.lastname: Lauritzen
authors.forename: Christoffer
authors.initials: C
authors.lastname: Laustsen
authors.forename: Per
authors.initials: P
authors.lastname: Åkeson
authors.forename: Jan H
authors.initials: JH
authors.lastname: Ardenkjær-Larsen
mesh_terms: D000818:Animals; D001711:Biotransformation; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002247:Carbon Isotopes; D007651:Keto Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007930:Leucine / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D000637:Transaminases / Q000378:metabolism*
chemical_list: D002247:Carbon Isotopes; D007651:Keto Acids; C013082:alpha-ketoisocaproic acid; D000637:Transaminases; C019798:branched-chain-amino-acid transaminase; D007930:Leucine