In vivo MRSI of hyperpolarized [1-13C]pyruvate metabolism in rat hepatocellular carcinoma

Moses M. Darpolor, Yi Fen Yen, Mei Sze Chua, Lei Xing, Regina H. Clarke-Katzenberg, Wenfang Shi, Dirk Mayer, Sonal Josan, Ralph E. Hurd, Adolf Pfefferbaum, Lasitha Senadheera, Samuel So, Lawrence V. Hofmann, Gary M. Glazer, Daniel M. Spielman

Research output: Contribution to journalArticlepeer-review

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 [1-13C]alanine in an orthotopic HCC using single-voxel hyperpolarized [1-13C]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 [1-13C]alanine and [1-13C]lactate after a bolus intravenous injection of [1-13C]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the results demonstrated that the metabolic fate of [1-13C]pyruvate conversion to [1-13C]alanine significantly superseded that of [1-13C]pyruvate conversion to [1-13C]lactate, potentially serving as a marker of HCC tumors.

Original languageEnglish (US)
Pages (from-to)506-513
Number of pages8
JournalNMR in biomedicine
Volume24
Issue number5
DOIs
StatePublished - Jun 2011

Keywords

  • Alanine transaminase
  • Hepatocellular carcinoma
  • Hyperpolarized three-dimensional C MRSI
  • [1-C]pyruvate

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

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