title: Optimisation of dynamic nuclear polarisation of [1-(13)C] pyruvate by addition of gadolinium-based contrast agents.
abstract: Dynamic nuclear polarisation (DNP) of carbon-13 ((13)C) enriched endogenous compounds provides a novel means for magnetic resonance imaging and spectroscopy of biological processes. Adding small amounts of gadolinium-based contrast agents (GBCAs) to the (13)C-enriched substrate matrix increases the amount of hyperpolarisation that can be achieved, but also may decrease the longitudinal relaxation time (T(1)) of the (13)C nucleus in solution. This study examined the effects of five different GBCA at concentrations of 0.5, 1, 2, and 3 mM on [1-(13)C]-enriched pyruvic acid. It was found that contrast agents with an open chain structure (Gadobenate dimeglumine, Gadopentetate dimeglumine, Gadodiamide) caused the largest enhancement (up to 82%) in solid state polarisation relative to solutions without GBCA. In the liquid state, T(1) of pyruvate decreased by as much as 62% and polarisation was much lower (70%) relative to solutions without GBCA added. Conversely, for GBCA with macrocyclic structures (Gadoterate meglumine, Gadoteridol), the solid state polarisation enhancement was only slightly less than the open chain GBCA, but enhanced polarisation was retained much better in the liquid state with minimal decrease in T(1) (25% at the highest GBCA concentrations). Near maximum polarisation in the solid state was obtained at a GBCA concentration of 2 mM, with a higher concentration of 3 mM producing minimal improvement. These results indicate that the macrocyclic contrast agents provide the best combination of high solid state and liquid state polarisations with minimal loss of T(1) in experiments with hyperpolarised (13)C-enriched pyruvate. This suggests that macrocyclic contrast agents should be the GBCA of choice for maximising signal in experiments with hyperpolarised (13)C-enriched pyruvate, particularly for in vivo measurements where shortened substrate T(1) is especially problematic.
authors.affiliation: Robarts Research Institute, London, Ontario, Canada N6A 5K8. lfriesen@imaging.robarts.ca
authors.forename: Lanette
authors.initials: L
authors.lastname: Friesen-Waldner
authors.forename: Albert
authors.initials: A
authors.lastname: Chen
authors.forename: Will
authors.initials: W
authors.lastname: Mander
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Scholl
authors.forename: Charles A
authors.initials: CA
authors.lastname: McKenzie
mesh_terms: D002247:Carbon Isotopes; D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D007553:Isotope Labeling; D019289:Pyruvic Acid / Q000737:chemistry*
chemical_list: D002247:Carbon Isotopes; D003287:Contrast Media; D019289:Pyruvic Acid; D005682:Gadolinium