title: Hyperpolarized [1,4-(13)C]-diethylsuccinate: a potential DNP substrate for in vivo metabolic imaging.
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-(13)C]-diethylsuccinate, for hyperpolarized (13)C 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), [(13)C]-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 (13)C metabolic imaging.
authors.affiliation: San Francisco State University, Department of Chemistry and Biochemistry, San Francisco, CA, USA.
authors.forename: Kelvin L
authors.initials: KL
authors.lastname: Billingsley
authors.forename: Sonal
authors.initials: S
authors.lastname: Josan
authors.forename: Jae Mo
authors.initials: JM
authors.lastname: Park
authors.forename: Sui Seng
authors.initials: SS
authors.lastname: Tee
authors.forename: Eleanor
authors.initials: E
authors.lastname: Spielman-Sun
authors.forename: Ralph
authors.initials: R
authors.lastname: Hurd
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
authors.forename: Daniel
authors.initials: D
authors.lastname: Spielman
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D045744:Cell Line, Tumor; D002952:Citric Acid Cycle; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D013386:Succinates; D013997:Time Factors
chemical_list: D002247:Carbon Isotopes; D013386:Succinates; C052819:diethyl succinate
keywords: dynamic nuclear polarization; hyperpolarized carbon-13; magnetic resonance spectroscopy; tricarboxylic acid cycle