| Real Time Molecular Imaging of TCA Cycle Metabolism <i>In Vivo</i> By Hyperpolarized 1-<sup>13</sup>C Diethyl Succinate. | |
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MedLine Citation:
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PMID: 22146049 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The Krebs tricarboxylic acid cycle (TCA) is central to metabolic energy production and is known to be altered in many disease states. Real time molecular imaging of TCA cycle <i>in</i> vivo will be important in understanding the metabolic basis of several diseases. Positron emission tomography (PET) using FDG-glucose (2-[<sup>18</sup>F]fluoro-2-deoxy-D-glucose) is already being used as a metabolic imaging agent in clinics. However, FDG-glucose does not reveal anything past glucose uptake and phosphorylation. We have developed a new metabolic imaging agent, hyperpolarized diethyl 1-<sup>13</sup>C 2,3-d<sub>2</sub> succinate, that allows for real time <i>in vivo</i> imaging and spectroscopy of the TCA cycle. Diethyl succinate can be hyperpolarized using parahydrogen induced polarization (PHIP) in an aqueous solution with signal enhancement of 5000 compared to Boltzmann polarization. <sup>13</sup>C magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) were achieved <i>in vivo</i> seconds after injection of 10 to 20 μmol of hyperpolarized diethyl succinate into normal mice. The downstream metabolites of hyperpolarized diethyl succinate were identified <i>in vivo</i> as malate, succinate, fumarate and aspartate. The metabolism of diethyl succinate was altered after exposing the animal to 3-nitropropionate, a known irreversible inhibitor of succinate dehydrogenase. Based on our results, hyperpolarized diethyl succinate allows for in real time <i>in vivo</i> MRI and MRS with a high signal to noise ratio and with visualization of multiple steps of the TCA cycle. Hyperpolarization of diethyl succinate and its <i>in vivo</i> applications may reveal an entirely new regime wherein the local status of TCA cycle metabolism is interrogated on the time scale of seconds to minutes with unprecedented chemical specificity and MR sensitivity. |
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Authors:
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Niki M Zacharias; Henry R Chan; Napapon Sailasuta; Brian D Ross; Pratip Bhattacharya |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-7 |
Journal Detail:
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Title: Journal of the American Chemical Society Volume: - ISSN: 1520-5126 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7503056 Medline TA: J Am Chem Soc Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
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