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 journalArticle

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the results demonstrated that the metabolic fate of [1-13C]pyruvate conversion to [1-13C]alanine significantly superseded that of [1-13C]pyruvate conversion to [1-13C]lactate, potentially serving as a marker of HCC tumors.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
Externally publishedYes

Fingerprint

Pyruvic Acid
Metabolism
Liver
Rats
Tumors
Hepatocellular Carcinoma
Alanine
Lactic Acid
Neoplasms
Bearings (structural)
Buffaloes
Polymerase chain reaction
Alanine Transaminase
NADP
Oxidoreductases
Tissue
Intravenous Injections
Messenger RNA
Real-Time Polymerase Chain Reaction
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Spectroscopy
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Darpolor, M. M., Yen, Y. F., Chua, M. S., Xing, L., Clarke-Katzenberg, R. H., Shi, W., ... Spielman, D. M. (2011). In vivo MRSI of hyperpolarized [1-13C]pyruvate metabolism in rat hepatocellular carcinoma. NMR in Biomedicine, 24(5), 506-513. https://doi.org/10.1002/nbm.1616

In vivo MRSI of hyperpolarized [1-13C]pyruvate metabolism in rat hepatocellular carcinoma. / Darpolor, Moses M.; Yen, Yi Fen; Chua, Mei Sze; Xing, Lei; Clarke-Katzenberg, Regina H.; Shi, Wenfang; Mayer, Dirk; Josan, Sonal; Hurd, Ralph E.; Pfefferbaum, Adolf; Senadheera, Lasitha; So, Samuel; Hofmann, Lawrence V.; Glazer, Gary M.; Spielman, Daniel M.

In: NMR in Biomedicine, Vol. 24, No. 5, 06.2011, p. 506-513.

Research output: Contribution to journalArticle

Darpolor, MM, Yen, YF, Chua, MS, Xing, L, Clarke-Katzenberg, RH, Shi, W, Mayer, D, Josan, S, Hurd, RE, Pfefferbaum, A, Senadheera, L, So, S, Hofmann, LV, Glazer, GM & Spielman, DM 2011, 'In vivo MRSI of hyperpolarized [1-13C]pyruvate metabolism in rat hepatocellular carcinoma', NMR in Biomedicine, vol. 24, no. 5, pp. 506-513. https://doi.org/10.1002/nbm.1616
Darpolor MM, Yen YF, Chua MS, Xing L, Clarke-Katzenberg RH, Shi W et al. In vivo MRSI of hyperpolarized [1-13C]pyruvate metabolism in rat hepatocellular carcinoma. NMR in Biomedicine. 2011 Jun;24(5):506-513. https://doi.org/10.1002/nbm.1616
Darpolor, Moses M. ; Yen, Yi Fen ; Chua, Mei Sze ; Xing, Lei ; Clarke-Katzenberg, Regina H. ; Shi, Wenfang ; Mayer, Dirk ; Josan, Sonal ; Hurd, Ralph E. ; Pfefferbaum, Adolf ; Senadheera, Lasitha ; So, Samuel ; Hofmann, Lawrence V. ; Glazer, Gary M. ; Spielman, Daniel M. / In vivo MRSI of hyperpolarized [1-13C]pyruvate metabolism in rat hepatocellular carcinoma. In: NMR in Biomedicine. 2011 ; Vol. 24, No. 5. pp. 506-513.
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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.",
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AU - Clarke-Katzenberg, Regina H.

AU - Shi, Wenfang

AU - Mayer, Dirk

AU - Josan, Sonal

AU - Hurd, Ralph E.

AU - Pfefferbaum, Adolf

AU - Senadheera, Lasitha

AU - So, Samuel

AU - Hofmann, Lawrence V.

AU - Glazer, Gary M.

AU - Spielman, Daniel M.

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