title: Synthesis and testing of a p-H2 hyperpolarized 13C probe based on the pyrazolo[1,5-a]pyrimidineacetamide DPA-713, an MRI vector to target the peripheral benzodiazepine receptors.
abstract: DPA-713 is the lead compound of a recently developed 2-phenylpyrazolo[1,5-a]pyrimidineacetamide series that has been shown to display a good targeting capability toward peripheral benzodiazepine receptors, recently renamed translocator protein (18 kDa) or in short TSPO. On the basis of this structure, a novel derivative bearing a [(13)C]butynoate moiety has been designed and synthesized (three steps-42% overall yield) providing, upon rapid and quantitative para-hydrogenation, the corresponding hyperpolarized [(13)C]alkene. Para-hydrogen-induced polarization effects have been detected in both (1)H and (13)C-NMR spectra. Upon applying a field cycling procedure, the spin order of para-H(2) added hydrogens is transferred on the (13)C carboxylate moiety yielding a signal enhancement of approximately 4500 times. T(1) of the carboxylate carbon atom is approximately 21.9 s (at 9.37 T). A (13)C-MR image has been acquired by using the (13)C RARE (Rapid Acquisition by Relaxation Enhancement) acquisition protocol on a 10-mM solution. The main limitation to the in vivo use of this novel para-hydrogenated [(13)C]derivative is its relatively low solubility in aqueous systems.
authors.affiliation: Dipartimento di Chimica IFM and Centro di Imaging Molecolare, Università degli Studi di Torino, Torino, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Cerutti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viale
authors.forename: Annelaure
authors.initials: A
authors.lastname: Damont
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dollé
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D002247:Carbon Isotopes / Q000032:analysis / Q000737:chemistry*; D002855:Chromatography, Thin Layer; D004952:Esters / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006859:Hydrogen / Q000737:chemistry / Q000378:metabolism*; D006865:Hydrogenation; D007553:Isotope Labeling / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D018079:Receptors, GABA / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D014867:Water
chemical_list: D000081:Acetamides; D002247:Carbon Isotopes; D004952:Esters; D058787:GABA-A Receptor Antagonists; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D018079:Receptors, GABA; C499229:TSPO protein, human; D014867:Water; D006859:Hydrogen