Imaging cerebral 2-ketoisocaproate metabolism with hyperpolarized 13C Magnetic Resonance Spectroscopic Imaging

被引：30
作者：
Butt, Sadia A. [3 ,4 ]
Sogaard, Lise V. [3 ]
Magnusson, Peter O. [3 ]
Lauritzen, Mette H. [3 ]
Laustsen, Christoffer [3 ,5 ,6 ]
Akeson, Per [3 ]
Ardenkjaer-Larsen, Jan H. [1 ,2 ]
机构：
[1] Tech Univ Denmark, Dept Elect Engn, DK-2800 Lyngby, Denmark
[2] GE Healthcare, DK-2605 Brondby, Denmark
[3] Copenhagen Univ Hosp, Danish Res Ctr Magnet Resonance, Hvidovre, Denmark
[4] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark
[5] Aarhus Univ Hosp, Inst Clin Med, MR Res Ctr, DK-8000 Aarhus, Denmark
[6] Aarhus Univ, Dept Chem, Ctr Insoluble Prot Struct inSPIN, DK-8000 Aarhus, Denmark
来源：
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2012年 / 32卷 / 08期
关键词：
BCAT; C-13; hyperpolarization; magnetic resonance; metabolism; BRANCHED-CHAIN AMINOTRANSFERASE; ALPHA-KETOISOCAPROIC ACID; BRAIN-BARRIER TRANSPORT; RAT-BRAIN; AMINO-ACIDS; ALZHEIMERS-DISEASE; MESSENGER-RNA; LACTATE; EXPRESSION; NEURONS;
D O I：
10.1038/jcbfm.2012.34
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
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-C-13]isocaproate (KIC) in the normal rat using magnetic resonance modalities. Hyperpolarized KIC is metabolized to [1-C-13]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. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 1508-1514; doi: 10.1038/jcbfm.2012.34; published online 28 March 2012
引用
收藏
页码：1508 / 1514
页数：7
相关论文
共 47 条
  • [1] Ardenkjar-Larsen Jan H, 2003, Discov Med, V3, P37
  • [2] Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain
    Bittar, PG
    Charnay, Y
    Pellerin, L
    Bouras, C
    Magistretti, PJ
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1996, 16 (06) : 1079 - 1089
  • [3] Characterization of the high-affinity monocarboxylate transporter MCT2 in Xenopus laevis oocytes
    Bröer, S
    Bröer, A
    Schneider, HP
    Stegen, C
    Halestrap, AP
    Deitmer, JW
    [J]. BIOCHEMICAL JOURNAL, 1999, 341 : 529 - 535
  • [4] Expression of cytosolic branched chain amino transferase (BCATc) mRNA in the developing mouse brain
    Castellano, Stefania
    Casarosa, Simona
    Sweatt, Andrew J.
    Hutson, Susan M.
    Bozzi, Yuri
    [J]. GENE EXPRESSION PATTERNS, 2007, 7 (04) : 485 - 490
  • [5] Hyperpolarized c-13 spectroscopic imaging of the TRAMP mouse at 3T - Initial experience
    Chen, Albert P.
    Albers, Mark J.
    Cunningham, Charles H.
    Kohler, Susan J.
    Yen, Yi-Fen
    Hurd, Ralph E.
    Tropp, James
    Bok, Robert
    Pauly, John M.
    Nelson, Sarah J.
    Kurhanewicz, John
    Vigneron, Daniel B.
    [J]. MAGNETIC RESONANCE IN MEDICINE, 2007, 58 (06) : 1099 - 1106
  • [6] KINETICS OF BLOOD-BRAIN-BARRIER TRANSPORT OF PYRUVATE, LACTATE AND GLUCOSE IN SUCKLING, WEANLING AND ADULT-RATS
    CREMER, JE
    CUNNINGHAM, VJ
    PARDRIDGE, WM
    BRAUN, LD
    OLDENDORF, WH
    [J]. JOURNAL OF NEUROCHEMISTRY, 1979, 33 (02) : 439 - 445
  • [7] Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy
    Day, Sam E.
    Kettunen, Mikko I.
    Gallagher, Ferdia A.
    Hu, De-En
    Lerche, Mathilde
    Wolber, Jan
    Golman, Klaes
    Ardenkjaer-Larsen, Jan Henrik
    Brindle, Kevin M.
    [J]. NATURE MEDICINE, 2007, 13 (11) : 1382 - 1387
  • [8] The low-affinity monocarboxylate transporter MCT4 is adapted to the export of lactate in highly glycolytic cells
    Dimmer, KS
    Friedrich, B
    Lang, F
    Deitmer, JW
    Bröer, S
    [J]. BIOCHEMICAL JOURNAL, 2000, 350 : 219 - 227
  • [9] Altered activities of rat brain metabolic enzymes in electroconvulsive shock-induced seizures
    Erakovic, V
    Zupan, G
    Varljen, J
    Laginja, J
    Simonic, A
    [J]. EPILEPSIA, 2001, 42 (02) : 181 - 189
  • [10] Widespread neuronal expression of branched-chain aminotransferase in the CNS:: implications for leucine/glutamate metabolism and for signaling by amino acids
    García-Espinosa, María A.
    Wallin, Reidar
    Hutson, Susan M.
    Sweatt, Andrew J.
    [J]. JOURNAL OF NEUROCHEMISTRY, 2007, 100 (06) : 1458 - 1468
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