Hyperpolarized [1,4‐13C]‐diethylsuccinate: a potential DNP substrate for in vivo metabolic imaging |
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| Authors: | Kelvin L. Billingsley Sonal Josan Jae Mo Park Sui Seng Tee Eleanor Spielman‐Sun Ralph Hurd Dirk Mayer Daniel Spielman |
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| Affiliation: | 1. San Francisco State University, Department of Chemistry and Biochemistry, , San Francisco, CA, USA;2. Stanford University, Department of Radiology, , Stanford, CA, USA;3. SRI International, Neuroscience Program, , Menlo Park, CA, USA;4. Oberlin College, Department of Chemistry, , Oberlin, OH, USA;5. GE Healthcare, Applied Sciences Laboratory, , Menlo Park, CA, USA;6. University of Maryland, Baltimore, Department of Diagnostic Radiology and Nuclear Medicine, , Baltimore, MD, USA;7. Stanford University, Department of Electrical Engineering, , Stanford, CA, USA |
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| Abstract: | The tricarboxylic acid (TCA) cycle performs an essential role in the regulation of energy and metabolism, and deficiencies in this pathway are commonly correlated with various diseases. However, the development of non‐invasive techniques for the assessment of the cycle in vivo has remained challenging. In this work, the applicability of a novel imaging agent, [1,4‐13C]‐diethylsuccinate, for hyperpolarized 13C metabolic imaging of the TCA cycle was explored. In vivo spectroscopic studies were conducted in conjunction with in vitro analyses to determine the metabolic fate of the imaging agent. Contrary to previous reports (Zacharias NM et al. J. Am. Chem. Soc. 2012; 134: 934–943), [13C]‐labeled diethylsuccinate was primarily metabolized to succinate‐derived products not originating from TCA cycle metabolism. These results illustrate potential issues of utilizing dialkyl ester analogs of TCA cycle intermediates as molecular probes for hyperpolarized 13C metabolic imaging. Copyright © 2014 John Wiley & Sons, Ltd. |
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| Keywords: | hyperpolarized carbon‐13 dynamic nuclear polarization magnetic resonance spectroscopy tricarboxylic acid cycle |
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