title: A platform for designing hyperpolarized magnetic resonance chemical probes.
abstract: Hyperpolarization is a highly promising technique for improving the sensitivity of magnetic resonance chemical probes. Here we report [(15)N, D(9)]trimethylphenylammonium as a platform for designing a variety of hyperpolarized magnetic resonance chemical probes. The platform structure shows a remarkably long (15)N spin-lattice relaxation value (816 s, 14.1 T) for retaining its hyperpolarized spin state. The extended lifetime enables the detection of the hyperpolarized (15)N signal of the platform for several tens of minutes and thus overcomes the intrinsic short analysis time of hyperpolarized probes. Versatility of the platform is demonstrated by applying it to three types of hyperpolarized chemical probes: one each for sensing calcium ions, reactive oxygen species (hydrogen peroxide) and enzyme activity (carboxyl esterase). All of the designed probes achieve high sensitivity with rapid reactions and chemical shift changes, which are sufficient to allow sensitive and real-time monitoring of target molecules by (15)N magnetic resonance.
authors.affiliation: INAMORI Frontier Research Center, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819 0395, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nonaka
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Hata
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Doura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nishihara
authors.forename: Keiko
authors.initials: K
authors.lastname: Kumagai
authors.forename: Mai
authors.initials: M
authors.lastname: Akakabe
authors.forename: Masashi
authors.initials: M
authors.lastname: Tsuda
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Sando
references.citation: J Am Chem Soc. 2008 Apr 9;130(14):4598-9
references.pmid: 18345678
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5503-7
references.pmid: 19276112
references.citation: Drug Discov Today. 2005 Mar 1;10(5):313-25
references.pmid: 15749280
references.citation: Contrast Media Mol Imaging. 2011 Nov-Dec;6(6):499-506
references.pmid: 22144028
references.citation: Chem Commun (Camb). 2012 Sep 14;48(71):8864-79
references.pmid: 22801420
references.citation: Invest Ophthalmol Vis Sci. 1998 Jun;39(7):1188-97
references.pmid: 9620079
references.citation: Chem Rev. 2010 May 12;110(5):3019-42
references.pmid: 20415475
references.citation: Psychopharmacology (Berl). 1987;92(3):278-84
references.pmid: 2957716
references.citation: Cardiovasc Res. 2005 Oct 1;68(1):26-36
references.pmid: 16009356
references.citation: J Am Chem Soc. 2009 Nov 11;131(44):16014-5
references.pmid: 19848401
references.citation: J Am Chem Soc. 2009 Dec 9;131(48):17591-6
references.pmid: 19860409
references.citation: J Am Chem Soc. 2003 Jul 16;125(28):8666-71
references.pmid: 12848574
references.citation: J Biol Chem. 1989 May 15;264(14):8171-8
references.pmid: 2498308
references.citation: Angew Chem Int Ed Engl. 2012 Mar 12;51(11):2731-5
references.pmid: 22311700
references.citation: J Am Chem Soc. 2004 Nov 3;126(43):14079-85
references.pmid: 15506772
references.citation: J Am Chem Soc. 2008 Nov 5;130(44):14533-43
references.pmid: 18841967
references.citation: J Am Chem Soc. 2011 Mar 23;133(11):3776-9
references.pmid: 21366297
references.citation: J Am Chem Soc. 2005 Nov 30;127(47):16652-9
references.pmid: 16305254
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18606-11
references.pmid: 22042839
references.citation: Angew Chem Int Ed Engl. 1999 Nov 2;38(21):3209-3212
references.pmid: 10556905
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21316-21
references.pmid: 21115844
references.citation: Nat Rev Mol Cell Biol. 2003 Jul;4(7):530-8
references.pmid: 12838336
references.citation: Contrast Media Mol Imaging. 2011 May-Jun;6(3):139-47
references.pmid: 21698772
references.citation: FEBS Lett. 2011 Oct 3;585(19):3133-8
references.pmid: 21907715
references.citation: Bioorg Med Chem Lett. 2012 Jun 1;22(11):3632-8
references.pmid: 22572577
references.citation: Curr Opin Chem Biol. 2010 Feb;14(1):90-6
references.pmid: 19913452
references.citation: Angew Chem Int Ed Engl. 2012 Oct 1;51(40):10114-7
references.pmid: 22961955
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 2;100(18):10158-63
references.pmid: 12930897
references.citation: Clin Biochem. 2011 Jul;44(10-11):849-52
references.pmid: 21515248
references.citation: Q J Nucl Med Mol Imaging. 2009 Dec;53(6):604-17
references.pmid: 20016452
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11270-5
references.pmid: 16837573
references.citation: Clin Cancer Res. 2002 Aug;8(8):2605-11
references.pmid: 12171891
references.citation: J Am Chem Soc. 2011 Aug 3;133(30):11795-801
references.pmid: 21692446
references.citation: Nature. 2008 Jun 12;453(7197):940-3
references.pmid: 18509335
references.citation: Anticancer Res. 2009 May;29(5):1551-5
references.pmid: 19443365
references.citation: Eur Radiol. 2006 Jan;16(1):57-67
references.pmid: 16402256
references.citation: Org Biomol Chem. 2005 Aug 7;3(15):2755-61
references.pmid: 16032354