In vivo and in vitro liver cancer metabolism observed with hyperpolarized [5-13C]glutamine

• Published in: Journal of magnetic resonance (1997) 2013-07, Vol.232, p.45-52
• Main Authors: Cabella, C., Karlsson, M., Canapè, C., Catanzaro, G., Colombo Serra, S., Miragoli, L., Poggi, L., Uggeri, F., Venturi, L., Jensen, P.R., Lerche, M.H., Tedoldi, F.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - metabolism; Carbon Isotopes; Cell Line, Tumor; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; Dynamic nuclear polarization; Glutaminase - metabolism; Glutamine; Glutamine - metabolism; Liver cancer; Liver Neoplasms, Experimental - drug therapy; Liver Neoplasms, Experimental - metabolism; Magnetic Resonance Spectroscopy - methods; Rats
• ISSN: 1090-7807; 1096-0856
• DOI: 10.1016/j.jmr.2013.04.010

[Display omitted] •A new and improved preparation of hyperpolarized [5-13C]glutamine is proposed.•This DNP preparation allows in vivo and in vitro MR to be successfully performed.•Signal of the metabolic product [5-13C]glutamate was detected in rat liver hepatoma.•It is possible to monitor response to chemotherapy with [5-13C]glutamine. 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 13C 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 [5-13C]glutamine, which provides a highly sensitive 13C MR marker. With this preparation of hyperpolarized [5-13C]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 [5-13C]glutamine used in tumour models warrant the new preparation to allow metabolic studies with this conditionally essential amino acid.