title: Parahydrogen-induced polarization of carboxylic acids: a pilot study of valproic acid and related structures.
abstract: Parahydrogen-induced polarization (PHIP) is a promising new tool for medical applications of MR, including MRI. The PHIP technique can be used to transfer high non-Boltzmann polarization, derived from parahydrogen, to isotopes with a low natural abundance or low gyromagnetic ratio (e.g. (13)C), thus improving the signal-to-noise ratio by several orders of magnitude. A few molecules acting as metabolic sensors have already been hyperpolarized with PHIP, but the direct hyperpolarization of drugs used to treat neurological disorders has not been accomplished until now. Here, we report on the first successful hyperpolarization of valproate (valproic acid, VPA), an important and commonly used antiepileptic drug. Hyperpolarization was confirmed by detecting the corresponding signal patterns in the (1)H NMR spectrum. To identify the optimal experimental conditions for the conversion of an appropriate VPA precursor, structurally related molecules with different side chains were analyzed in different solvents using various catalytic systems. The presented results include hyperpolarized (13)C NMR spectra and proton images of related systems, confirming their applicability for MR studies. PHIP-based polarization enhancement may provide a new MR technique to monitor the spatial distribution of valproate in brain tissue and to analyze metabolic pathways after valproate administration.
authors.affiliation: Leibniz Institute for Neurobiology, Magdeburg, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Lego
authors.forename: Markus
authors.initials: M
authors.lastname: Plaumann
authors.forename: Thomas
authors.initials: T
authors.lastname: Trantzschel
authors.forename: Joachim
authors.initials: J
authors.lastname: Bargon
authors.forename: Henning
authors.initials: H
authors.lastname: Scheich
authors.forename: Gerd
authors.initials: G
authors.lastname: Buntkowsky
authors.forename: Torsten
authors.initials: T
authors.lastname: Gutmann
authors.forename: Grit
authors.initials: G
authors.lastname: Sauer
authors.forename: Johannes
authors.initials: J
authors.lastname: Bernarding
authors.forename: Ute
authors.initials: U
authors.lastname: Bommerich
mesh_terms: D002384:Catalysis; D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D010865:Pilot Projects; D066244:Proton Magnetic Resonance Spectroscopy; D012815:Signal Processing, Computer-Assisted; D014635:Valproic Acid / Q000737:chemistry*
chemical_list: C551394:2-hexyl-4-pentynoic acid; D005231:Fatty Acids, Unsaturated; C003879:4-pentynoic acid; D014635:Valproic Acid; D006859:Hydrogen
keywords: 13C NMR; 1H MRI; PHIP; polarization transfer; valproic acid