Ferdia Aidan Gallagher BMBCh, Presenter: Research funded, General Electric Company

Sam Day, Abstract Co-Author: Research support, General Electric Company

Mikko I. Kettunen, Abstract Co-Author: Research support, General Electric Company

Jan Wolber, Abstract Co-Author: Employee, General Electric Company

Jan-Henrik Ardenkjaer-Larsen, Abstract Co-Author: Employee, General Electric Company

Kevin M. Brindle, Abstract Co-Author: Research funded, General Electric Company

Dynamic nuclear polarization (DNP) has recently emerged as a technique for dramatically increasing the signal-to-noise in carbon-13 magnetic resonance spectroscopy (MRS) by 10,000-fold or more. Administration of hyperpolarized 13C-labeled molecules allows in vitro and in vivo spectroscopic imaging of their metabolic fate. In this study we have used this technique to monitor glutamine utilization, which plays a central metabolic role in many cells including tumors and neuronal tissues.

[5-13C1]glutamine was polarized using DNP to levels of up to 5%, representing a 6000-fold increase in signal as compared to thermal equilibrium polarization. Hyperpolarized glutamine was injected into media containing hepatoma cells (HepG2) grown on cytodex microcarrier beads. Real-time 13C MRS was used to follow transfer of the hyperpolarized 13C label from glutamine to glutamate, a reaction catalyzed by the mitochondrial enzyme, glutaminase.

Metabolism of hyperpolarized [5-13C1]glutamine to [5-13C1]glutamate was demonstrated over the first minute following injection of the labeled glutamine into the cell suspension. Thermal equilibrium spectra acquired shortly after the injection confirmed rapid metabolism of the labeled glutamine to glutamate. The rate of metabolism was reduced by co-administration of unlabeled glutamine or alanine, both of which inhibit glutamine uptake into the cell. The reaction was also inhibited by 6-diazo-5-oxonorleucine (DON), a known inhibitor of glutaminase.

This study demonstrates that conversion of glutamine to glutamate can be followed in real-time using DNP. The technique allows the measurement of an intramitochondrial enzyme-catalyzed reaction in intact cells using MRS.

This technique may provide a way of imaging glutamine metabolism in vivo in tumors. Since this has been correlated with tumor growth, it may allow early detection of response to chemotherapy.

Gallagher, F, Day, S, Kettunen, M, Wolber, J, Ardenkjaer-Larsen, J, Brindle, K, Real-time Visualization of Hyperpolarized ¹³C-labeled Glutamine Metabolism in Human Hepatoma Cells Using Magnetic Resonance Spectroscopy.  Radiological Society of North America 2007 Scientific Assembly and Annual Meeting, November 25 - November 30, 2007 ,Chicago IL. http://archive.rsna.org/2007/5001567.html