title: Rapid sequential injections of hyperpolarized [1-¹³C]pyruvate in vivo using a sub-kelvin, multi-sample DNP polarizer.
abstract: The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of (13)C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-(13)C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5 min interval between injections of hyperpolarized [1-(13)C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1 min after administration, and 6 min after administration. Dramatic increases in (13)C-bicarbonate were detected just 1 min (as well as 6 min) after DCA administration.
authors.affiliation: Dept. of Radiology and Biomedical Imaging, Box 2512, University of California, San Francisco, 1700 4th St. QB3 Building, Suite 102, San Francisco, CA 94158-2512, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Hu
authors.forename: Peder E Z
authors.initials: PE
authors.lastname: Larson
authors.forename: Mark
authors.initials: M
authors.lastname: Vancriekinge
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Leach
authors.forename: Ilwoo
authors.initials: I
authors.lastname: Park
authors.forename: Christine
authors.initials: C
authors.lastname: Leon
authors.forename: Jenny
authors.initials: J
authors.lastname: Zhou
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Shin
authors.forename: Galen
authors.initials: G
authors.lastname: Reed
authors.forename: Paul
authors.initials: P
authors.lastname: Keselman
authors.forename: Cornelius
authors.initials: C
authors.lastname: von Morze
authors.forename: Hikari
authors.initials: H
authors.lastname: Yoshihara
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bok
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nelson
authors.forename: John
authors.initials: J
authors.lastname: Kurhanewicz
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Vigneron
mesh_terms: D000818:Animals; D002247:Carbon Isotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D003999:Dichloroacetic Acid / Q000493:pharmacokinetics*; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008657:Metabolic Clearance Rate; D057054:Molecular Imaging / Q000379:methods*; D009928:Organ Specificity; D019289:Pyruvic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D002247:Carbon Isotopes; D019289:Pyruvic Acid; D003999:Dichloroacetic Acid