title: Hyperpolarized (13)C Magnetic Resonance and Its Use in Metabolic Assessment of Cultured Cells and Perfused Organs.
abstract: Diseased tissue is often characterized by abnormalities in intermediary metabolism. Observing these alterations in situ may lead to an improved understanding of pathological processes and novel ways to monitor these processes noninvasively in human patients. Although (13)C is a stable isotope safe for use in animal models of disease as well as human subjects, its utility as a metabolic tracer has largely been limited to ex vivo analyses employing analytical techniques like mass spectrometry or nuclear magnetic resonance spectroscopy. Neither of these techniques is suitable for noninvasive metabolic monitoring, and the low abundance and poor gyromagnetic ratio of conventional (13)C make it a poor nucleus for imaging. However, the recent advent of hyperpolarization methods, particularly dynamic nuclear polarization (DNP), makes it possible to enhance the spin polarization state of (13)C by many orders of magnitude, resulting in a temporary amplification of the signal sufficient for monitoring kinetics of enzyme-catalyzed reactions in living tissue through magnetic resonance spectroscopy or magnetic resonance imaging. Here, we review DNP techniques to monitor metabolism in cultured cells, perfused hearts, and perfused livers, focusing on our experiences with hyperpolarized [1-(13)C]pyruvate. We present detailed approaches to optimize the DNP procedure, streamline biological sample preparation, and maximize detection of specific metabolic activities. We also discuss practical aspects in the choice of metabolic substrates for hyperpolarization studies and outline some of the current technical and conceptual challenges in the field, including efforts to use hyperpolarization to quantify metabolic rates in vivo.
authors.affiliation: Department of Physics, University of Texas at Dallas, Richardson, Texas, USA. Electronic address: lloyd.lumata@utdallas.edu.
authors.forename: Lloyd
authors.initials: L
authors.lastname: Lumata
authors.affiliation: Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Chendong
authors.initials: C
authors.lastname: Yang
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Mukundan
authors.initials: M
authors.lastname: Ragavan
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Carpenter
authors.affiliation: Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address: ralph.deberardinis@utsouthwestern.edu.
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: DeBerardinis
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Electronic address: matthew.merritt@utsouthwestern.edu.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Merritt
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D002478:Cells, Cultured; D006801:Humans; D000067268:Isolated Heart Preparation; D007553:Isotope Labeling; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008660:Metabolism; D051379:Mice; D023421:Models, Animal; D019289:Pyruvic Acid
chemical_list: D002247:Carbon Isotopes; D019289:Pyruvic Acid
keywords: Cancer metabolism; Carbon-13; Hyperpolarization; Imaging; Metabolic flux; Nuclear magnetic resonance; Pyruvate; Warburg effect