All Publications


  • Hyperpolarized Sodium [1-C-13]-Glycerate as a Probe for Assessing Glycolysis In Vivo JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Park, J., Wu, M., Datta, K., Liu, S., Castillo, A., Lough, H., Spielman, D. M., Billingsley, K. L. 2017; 139 (19): 6629–34

    Abstract

    Hyperpolarized 13C magnetic resonance spectroscopy (MRS) provides unprecedented opportunities to obtain clinical diagnostic information through in vivo monitoring of metabolic pathways. The continuing advancement of this field relies on the identification of molecular probes that can effectively interrogate pathways critical to disease. In this report, we describe the synthesis, development, and in vivo application of sodium [1-13C]-glycerate ([13C]-Glyc) as a novel probe for evaluating glycolysis using hyperpolarized 13C MRS. This agent was prepared by a concise synthetic route and formulated for dynamic nuclear polarization. [13C]-Glyc displayed a high level of polarization and long spin-lattice relaxation time-both of which are necessary for future clinical investigations. In vivo spectroscopic studies with hyperpolarized [13C]-Glyc in rat liver furnished metabolic products, [13C]-labeled pyruvate and lactate, originating from glycolysis. The levels of production and relative intensities of these metabolites were directly correlated with the induced glycolytic state (fasted versus fed groups). This work establishes hyperpolarized [13C]-Glyc as a novel agent for clinically relevant 13C MRS studies of energy metabolism and further provides opportunities for evaluating intracellular redox states in biochemical investigations.

    View details for PubMedID 28467066

  • Doublet asymmetry for estimating polarization in hyperpolarized C-13-pyruvate studies NMR IN BIOMEDICINE Datta, K., Spielman, D. M. 2017; 30 (2)

    Abstract

    Hyperpolarized (13) C MRS allows in vivo interrogation of key metabolic pathways, with pyruvate (Pyr) the substrate of choice for current clinical studies. Knowledge of the liquid-state polarization is needed for full quantitation, and asymmetry of the C2 doublet, arising from 1% naturally abundant [1,2-(13) C]Pyr in any hyperpolarized [1-(13) C]Pyr sample, has been suggested as a direct measure of in vivo C1 polarization via the use of an in vitro calibration curve. Here we show that different polarization levels can yield the same C2 -doublet asymmetry, thus limiting the utility of this metric for quantitation. Furthermore, although the time evolution of doublet asymmetry is poorly modeled using the expected dominant relaxation mechanisms of carbon-proton dipolar coupling and chemical shift anisotropy, the inclusion of a C-C dipolar coupling term can explain the observed initial evolution of the C2 doublet asymmetry beyond its expected thermal equilibrium value.

    View details for DOI 10.1002/nbm.3670

    View details for Web of Science ID 000397274200003

    View details for PubMedCentralID PMC5330392

  • C-pyruvate studies. NMR in biomedicine Datta, K., Spielman, D. M. 2017; 30 (2)

    Abstract

    Hyperpolarized (13) C MRS allows in vivo interrogation of key metabolic pathways, with pyruvate (Pyr) the substrate of choice for current clinical studies. Knowledge of the liquid-state polarization is needed for full quantitation, and asymmetry of the C2 doublet, arising from 1% naturally abundant [1,2-(13) C]Pyr in any hyperpolarized [1-(13) C]Pyr sample, has been suggested as a direct measure of in vivo C1 polarization via the use of an in vitro calibration curve. Here we show that different polarization levels can yield the same C2 -doublet asymmetry, thus limiting the utility of this metric for quantitation. Furthermore, although the time evolution of doublet asymmetry is poorly modeled using the expected dominant relaxation mechanisms of carbon-proton dipolar coupling and chemical shift anisotropy, the inclusion of a C-C dipolar coupling term can explain the observed initial evolution of the C2 doublet asymmetry beyond its expected thermal equilibrium value.

    View details for DOI 10.1002/nbm.3670

    View details for PubMedID 28004867