In vivo measurement of normal rat intracellular pyruvate and lactate levels after injection of hyperpolarized [1-13 C]alanine

• Published in: Magnetic resonance imaging Vol. 29; no. 8; pp. 1035 - 1040
• Main Authors: Hu, Simon, Zhu, Minhua, Yoshihara, Hikari A.I, Wilson, David M, Keshari, Kayvan R, Shin, Peter, Reed, Galen, von Morze, Cornelius, Bok, Robert, Larson, Peder E.Z, Kurhanewicz, John, Vigneron, Daniel B
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.10.2011
• Subjects: Alanine - metabolism; Animals; Carbon Isotopes - metabolism; Dynamic nuclear polarization (DNP); Hyperpolarized carbon-13; Image Processing, Computer-Assisted - methods; Kinetics; Lactic Acid - metabolism; Magnetic Resonance Spectroscopy - methods; Magnetic resonance spectroscopy/spectroscopic imaging; Male; Monocarboxylate transporter (MCT); Monocarboxylic Acid Transporters - metabolism; Pyruvic Acid - metabolism; Radiology; Rats; Rats, Sprague-Dawley; Signal-To-Noise Ratio; Magnetic resonance spectroscopy/spectroscopic imaging; Hyperpolarized carbon-13; Dynamic nuclear polarization (DNP); Monocarboxylate transporter (MCT)
• ISSN: 0730-725X; 1873-5894
• DOI: 10.1016/j.mri.2011.07.001

Abstract Hyperpolarized technology utilizing dynamic nuclear polarization has enabled rapid and high-sensitivity measurements of13 C metabolism in vivo. The most commonly used in vivo agent for hyperpolarized13 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 of13 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.