title: In vivo measurement of normal rat intracellular pyruvate and lactate levels after injection of hyperpolarized [1-(13)C]alanine.
abstract: Hyperpolarized technology utilizing dynamic nuclear polarization has enabled rapid and high-sensitivity measurements of (13)C metabolism in vivo. The most commonly used in vivo agent for hyperpolarized (13)C metabolic imaging thus far has been [1-(13)C]pyruvate. In preclinical studies, not only is its uptake detected, but also its intracellular enzymatic conversion to metabolic products including [1-(13)C]lactate and [1-(13)C]alanine. However, the ratio of (13)C-lactate/(13)C-pyruvate measured in this data does not accurately reflect cellular values since much of the [1-(13)C]pyruvate is extracellular depending on timing, vascular properties, and extracellular space and monocarboxylate transporter activity. In order to measure the relative levels of intracellular pyruvate and lactate, in this project we hyperpolarized [1-(13)C]alanine and monitored the in vivo conversion to [1-(13)C]pyruvate and then the subsequent conversion to [1-(13)C]lactate. The intracellular lactate-to-pyruvate ratio of normal rat tissue measured with hyperpolarized [1-(13)C]alanine was 4.89±0.61 (mean±S.E.) as opposed to a ratio of 0.41±0.03 when hyperpolarized [1-(13)C]pyruvate was injected.
authors.affiliation: Department of Radiology and Biomedical Imaging, Box 2512, University of California, San Francisco, CA 94158-2512, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Hu
authors.forename: Minhua
authors.initials: M
authors.lastname: Zhu
authors.forename: Hikari A I
authors.initials: HA
authors.lastname: Yoshihara
authors.forename: David M
authors.initials: DM
authors.lastname: Wilson
authors.forename: Kayvan R
authors.initials: KR
authors.lastname: Keshari
authors.forename: Peter
authors.initials: P
authors.lastname: Shin
authors.forename: Galen
authors.initials: G
authors.lastname: Reed
authors.forename: Cornelius
authors.initials: C
authors.lastname: von Morze
authors.forename: Robert
authors.initials: R
authors.lastname: Bok
authors.forename: Peder E Z
authors.initials: PE
authors.lastname: Larson
authors.forename: John
authors.initials: J
authors.lastname: Kurhanewicz
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Vigneron
mesh_terms: D000409:Alanine / Q000378:metabolism*; D000818:Animals; D002247:Carbon Isotopes / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D059629:Signal-To-Noise Ratio
chemical_list: D002247:Carbon Isotopes; D027501:Monocarboxylic Acid Transporters; D019344:Lactic Acid; D019289:Pyruvic Acid; D000409:Alanine