title: In vivo MRSI of hyperpolarized [1-(13)C]pyruvate metabolism in rat hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC), the primary form of human adult liver malignancy, is a highly aggressive tumor with average survival rates that are currently less than 1 year following diagnosis. Most patients with HCC are diagnosed at an advanced stage, and no efficient marker exists for the prediction of prognosis and/or response(s) to therapy. We have reported previously a high level of [1-(13)C]alanine in an orthotopic HCC using single-voxel hyperpolarized [1-(13)C]pyruvate MRS. In the present study, we implemented a three-dimensional MRSI sequence to investigate this potential hallmark of cellular metabolism in rat livers bearing HCC (n = 7 buffalo rats). In addition, quantitative real-time polymerase chain reaction was used to determine the mRNA levels of lactate dehydrogenase A, nicotinamide adenine (phosphate) dinucleotide dehydrogenase quinone 1 and alanine transaminase. The enzyme levels were significantly higher in tumor than in normal liver tissues within each rat, and were associated with the in vivo MRSI signal of [1-(13)C]alanine and [1-(13)C]lactate after a bolus intravenous injection of [1-(13)C]pyruvate. Histopathological analysis of these tumors confirmed the successful growth of HCC as a nodule in buffalo rat livers, revealing malignancy and hypervascular architecture. More importantly, the results demonstrated that the metabolic fate of [1-(13)C]pyruvate conversion to [1-(13)C]alanine significantly superseded that of [1-(13)C]pyruvate conversion to [1-(13)C]lactate, potentially serving as a marker of HCC tumors.
authors.affiliation: Department of Radiology, Stanford University, Stanford, CA 94305-5488, USA. mdarpolor@gmail.com
authors.forename: Moses M
authors.initials: MM
authors.lastname: Darpolor
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Yen
authors.forename: Mei-Sze
authors.initials: MS
authors.lastname: Chua
authors.forename: Lei
authors.initials: L
authors.lastname: Xing
authors.forename: Regina H
authors.initials: RH
authors.lastname: Clarke-Katzenberg
authors.forename: Wenfang
authors.initials: W
authors.lastname: Shi
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
authors.forename: Sonal
authors.initials: S
authors.lastname: Josan
authors.forename: Ralph E
authors.initials: RE
authors.lastname: Hurd
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
authors.forename: Lasitha
authors.initials: L
authors.lastname: Senadheera
authors.forename: Samuel
authors.initials: S
authors.lastname: So
authors.forename: Lawrence V
authors.initials: LV
authors.lastname: Hofmann
authors.forename: Gary M
authors.initials: GM
authors.lastname: Glazer
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Spielman
mesh_terms: D000409:Alanine / Q000378:metabolism; D000818:Animals; D002247:Carbon Isotopes; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002247:Carbon Isotopes; D019344:Lactic Acid; D019289:Pyruvic Acid; D000409:Alanine