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In vivo MRSI of hyperpolarized [1-(13)C]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.
NMR Biomed; 24(5): 506-13, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21674652
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the results demonstrated that the metabolic fate of [1-(13)C]pyruvate conversion to [1-(13)C]alanine significantly superseded that of [1-(13)C]pyruvate conversion to [1-(13)C]lactate, potentially serving as a marker of HCC tumors.
Selo DaSilva