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Yoshihara H.A.I.,Ecole Polytechnique Federale de Lausanne | Can E.,Ecole Polytechnique Federale de Lausanne | Karlsson M.,Albeda Research Aps | Karlsson M.,Technical University of Denmark | And 4 more authors.
Physical Chemistry Chemical Physics | Year: 2016

[1-13C]pyruvate is the most widely used hyperpolarized metabolic magnetic resonance imaging agent. Using a custom-built 7.0 T polarizer operating at 1.0 K and trityl radical-doped [1-13C]pyruvic acid, unextrapolated solution-state 13C polarization greater than 60% was measured after dissolution and rapid transfer to a spectrometer magnet, demonstrating the signal enhancement attainable using optimized hardware. Slower rates of polarization under these conditions can be largely overcome with higher radical concentrations. © 2016 the Owner Societies. Source


Christensen C.E.,Albeda Innovation Aps | Christensen C.E.,Copenhagen University | Karlsson M.,Albeda Research Aps | Winther J.R.,Copenhagen University | And 2 more authors.
Journal of Biological Chemistry | Year: 2014

Background: Free cytosolic [NAD+]/[NADH] ratio maintains cellular redox homeostasis and is a cellular metabolic readout. Results: Pyruvate/lactate ratios show distinct metabolic phenotypes and are used to derive free cytosolic [NAD+]/[NADH] ratios. Conclusion: Determination of free cytosolic [NAD+]/[NADH] ratios using hyperpolarized glucose is applicable to a wide selection of cell types. Significance: This metabolic phenotyping may be a crucial tool to understand pathologies, and to diagnose and measure effects of therapies. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Source


Canape C.,University of Turin | Catanzaro G.,Bracco Imaging Spa | Terreno E.,University of Turin | Karlsson M.,Albeda Research Aps | And 2 more authors.
Magnetic Resonance in Medicine | Year: 2015

Purpose The correlation between glutamine metabolism and oncogene expression in cancers has led to a renewed interest in the role of glutamine in cancer cell survival. Hyperpolarized [5-13C]glutamine is evaluated as a potential biomarker for noninvasive metabolic measurements of drug response in prostate cancer cells. Methods Hyperpolarized [5-13C]glutamine is used to measure glutamine metabolism in two prostate cancer cell lines (PC3 and DU145) before and after treatment with the two natural anticancer drugs resveratrol and sulforaphane. An invasive biochemical assay simulating the hyperpolarized experiment is used to independently quantify glutamine metabolism. Results Glutamine metabolism is found to be 4 times higher in the more glutaminolytic DU145 cells compared with PC3 cells under proliferating growth conditions by using hyperpolarized [5-13C]glutamine as a noninvasive probe. A significant decrease in glutamine metabolism occurs upon apoptotic response to treatment with resveratrol and sulforaphane. Conclusion Hyperpolarized NMR using [5-13C]glutamine as a probe permits the noninvasive observation of glutaminolysis in different cell lines and under different treatment conditions. Hyperpolarized [5-13C]glutamine metabolism thus is a promising biomarker for the noninvasive detection of tumor response to treatment, as it directly monitors one of the hallmarks in cancer metabolism - glutaminolysis - in living cells. Magn Reson Med 73:2296-2305, 2015. © 2014 Wiley Periodicals, Inc. Source


Cabella C.,Bracco Imaging Spa | Karlsson M.,Albeda Research Aps | Canape C.,University of Turin | Catanzaro G.,Bracco Imaging Spa | And 8 more authors.
Journal of Magnetic Resonance | Year: 2013

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. © 2013 Elsevier Inc. Source

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