super(13)C magnetic resonance spectroscopy measurements with hyperpolarized [1- super(13)C] pyruvate can be used to detect the expression of transgenic pyruvate decarboxylase activity in vivo

Purpose Dissolution dynamic nuclear polarization can increase the sensitivity of the super(13)C magnetic resonance spectroscopy experiment by at least four orders of magnitude and offers a novel approach to the development of MRI gene reporters based on enzymes that metabolize super(13)C-labeled tra...

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Published in:Magnetic resonance in medicine 2016-08, Vol.76 (2), p.391-401
Main Authors: Dzien, Piotr, Tee, Sui-Seng, Kettunen, Mikko I, Lyons, Scott K, Larkin, Timothy J, Timm, Kerstin N, Hu, De-En, Wright, Alan, Rodrigues, Tiago B, Serrao, Eva M, Marco-Rius, Irene, Mannion, Elizabeth, D'Santos, Paula, Kennedy, Brett WC, Brindle, Kevin M
Format: Article
Language:English
Subjects:
Zymomonas mobilis
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Summary:Purpose Dissolution dynamic nuclear polarization can increase the sensitivity of the super(13)C magnetic resonance spectroscopy experiment by at least four orders of magnitude and offers a novel approach to the development of MRI gene reporters based on enzymes that metabolize super(13)C-labeled tracers. We describe here a gene reporter based on the enzyme pyruvate decarboxylase (EC 4.1.1.1), which catalyzes the decarboxylation of pyruvate to produce acetaldehyde and carbon dioxide. Methods Pyruvate decarboxylase from Zymomonas mobilis (zmPDC) and a mutant that lacked enzyme activity were expressed using an inducible promoter in human embryonic kidney (HEK293T) cells. Enzyme activity was measured in the cells and in xenografts derived from the cells using super(13)C MRS measurements of the conversion of hyperpolarized [1- super(13)C] pyruvate to H super(13) [Formulaomitted]. Results Induction of zmPDC expression in the cells and in the xenografts derived from them resulted in an approximately two-fold increase in the H super(13) [Formulaomitted]/[1- super(13)C] pyruvate signal ratio following intravenous injection of hyperpolarized [1- super(13)C] pyruvate. Conclusion We have demonstrated the feasibility of using zmPDC as an in vivo reporter gene for use with hyperpolarized super(13)C MRS. Magn Reson Med 76:391-401, 2016. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
ISSN:0740-3194
1522-2594
DOI:10.1002/mrm.25879