title: In vivo and in vitro liver cancer metabolism observed with hyperpolarized [5-(13)C]glutamine.
abstract: Glutamine metabolism is, with its many links to oncogene expression, considered a crucial step in cancer metabolism and it is thereby a key target for alteration in cancer development. In particular, strong correlations have been reported between oncogene expression and expression and activity of the enzyme glutaminase. This mitochondrial enzyme, which is responsible for the deamidation of glutamine to form glutamate, is overexpressed in many tumour tissues. In animal models, glutaminase expression is correlated with tumour growth rate and it is readily possible to limit tumour growth by suppression of glutaminase activity. In principle, hyperpolarized (13)C MR spectroscopy can provide insight to glutamine metabolism and should hence be a valuable tool to study changes in glutaminase activity as tumours progress. However, no such successful in vivo studies have been reported, even though several good biological models have been tested. This may, at least partly, be due to problems in preparing glutamine for hyperpolarization. This paper reports a new and improved preparation of hyperpolarized [5-(13)C]glutamine, which provides a highly sensitive (13)C MR marker. With this preparation of hyperpolarized [5-(13)C]glutamine, glutaminase activity in vivo in a rat liver tumour was investigated. Moreover, this marker was also used to measure response to drug treatment in vitro in cancer cells. These examples of [5-(13)C]glutamine used in tumour models warrant the new preparation to allow metabolic studies with this conditionally essential amino acid.
authors.affiliation: Centro Ricerche Bracco, Bracco Imaging Spa, Via Ribes 5, 10010 Colleretto Giacosa (TO), Italy. claudia.cabella@bracco.com
authors.forename: C
authors.initials: C
authors.lastname: Cabella
authors.forename: M
authors.initials: M
authors.lastname: Karlsson
authors.forename: C
authors.initials: C
authors.lastname: Canapè
authors.forename: G
authors.initials: G
authors.lastname: Catanzaro
authors.forename: S
authors.initials: S
authors.lastname: Colombo Serra
authors.forename: L
authors.initials: L
authors.lastname: Miragoli
authors.forename: L
authors.initials: L
authors.lastname: Poggi
authors.forename: F
authors.initials: F
authors.lastname: Uggeri
authors.forename: L
authors.initials: L
authors.lastname: Venturi
authors.forename: P R
authors.initials: PR
authors.lastname: Jensen
authors.forename: M H
authors.initials: MH
authors.lastname: Lerche
authors.forename: F
authors.initials: F
authors.lastname: Tedoldi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002247:Carbon Isotopes; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051381:Rats; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002247:Carbon Isotopes; D005973:Glutamine; D003841:Deoxycytidine; D005972:Glutaminase; D000093542:Gemcitabine