TY - JOUR
T1 - Hyperpolarized 13C Magnetic Resonance and Its Use in Metabolic Assessment of Cultured Cells and Perfused Organs
AU - Lumata, Lloyd
AU - Yang, Chendong
AU - Ragavan, Mukundan
AU - Carpenter, Nicholas
AU - DeBerardinis, Ralph J.
AU - Merritt, Matthew E.
PY - 2015/9/9
Y1 - 2015/9/9
N2 - 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 13C 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 13C 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 13C 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 [1-13C]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.
AB - 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 13C 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 13C 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 13C 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 [1-13C]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.
KW - Cancer metabolism
KW - Carbon-13
KW - Hyperpolarization
KW - Imaging
KW - Metabolic flux
KW - Nuclear magnetic resonance
KW - Pyruvate
KW - Warburg effect
UR - http://www.scopus.com/inward/record.url?scp=84941025403&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84941025403&partnerID=8YFLogxK
U2 - 10.1016/bs.mie.2015.04.006
DO - 10.1016/bs.mie.2015.04.006
M3 - Article
C2 - 26358902
AN - SCOPUS:84941025403
SN - 0076-6879
VL - 561
SP - 73
EP - 106
JO - Methods in Enzymology
JF - Methods in Enzymology
ER -