Hyperpolarized Sodium [1-13C]-Glycerate as a Probe for Assessing Glycolysis In Vivo

Journal of the American Chemical Society

5 years ago

Hyperpolarized Sodium [1-13C]-Glycerate as a Probe for Assessing Glycolysis In Vivo

Heather Lough, Kelvin L. Billingsley, Marvin Wu, Shie-Chau Liu, Daniel M. Spielman, Jae Mo Park, Keshav Datta, Andrew Castillo

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.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b00708

DOI: 10.1021/jacs.7b00708