title: Metal ion sensing using ion chemical exchange saturation transfer 19F magnetic resonance imaging.
abstract: Although metal ions are involved in a myriad of biological processes, noninvasive detection of free metal ions in deep tissue remains a formidable challenge. We present an approach for specific sensing of the presence of Ca(2+) in which the amplification strategy of chemical exchange saturation transfer (CEST) is combined with the broad range of chemical shifts found in (19)F NMR spectroscopy to obtain magnetic resonance images of Ca(2+). We exploited the chemical shift change (Δω) of (19)F upon binding of Ca(2+) to the 5,5'-difluoro derivative of 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F-BAPTA) by radiofrequency labeling at the Ca(2+)-bound (19)F frequency and detection of the label transfer to the Ca(2+)-free (19)F frequency. Through the substrate binding kinetics we were able to amplify the signal of Ca(2+) onto free 5F-BAPTA and thus indirectly detect low Ca(2+) concentrations with high sensitivity.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Amnon
authors.initials: A
authors.lastname: Bar-Shir
authors.forename: Assaf A
authors.initials: AA
authors.lastname: Gilad
authors.forename: Kannie W Y
authors.initials: KW
authors.lastname: Chan
authors.forename: Guanshu
authors.initials: G
authors.lastname: Liu
authors.forename: Peter C M
authors.initials: PC
authors.lastname: van Zijl
authors.forename: Jeff W M
authors.initials: JW
authors.lastname: Bulte
authors.forename: Michael T
authors.initials: MT
authors.lastname: McMahon
mesh_terms: D002118:Calcium / Q000032:analysis* / Q000737:chemistry; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011522:Protons
chemical_list: D011522:Protons; D004533:Egtazic Acid; C039877:5,5'-difluoro-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium
references.citation: Angew Chem Int Ed Engl. 2012 Apr 23;51(17):4100-3
references.pmid: 22411775
references.citation: Biochim Biophys Acta. 1990 Dec 6;1020(3):290-304
references.pmid: 2248962
references.citation: Biochemistry. 1980 May 27;19(11):2396-404
references.pmid: 6770893
references.citation: Annu Rev Neurosci. 1989;12:227-53
references.pmid: 2648950
references.citation: Magn Reson Med. 2006 Apr;55(4):836-47
references.pmid: 16506187
references.citation: Chem Rev. 2008 May;108(5):1550-64
references.pmid: 18447377
references.citation: Magn Reson Med. 2012 Apr;67(4):1106-13
references.pmid: 22392814
references.citation: NMR Biomed. 2011 Feb;24(2):114-29
references.pmid: 20842758
references.citation: Biochem J. 2000 Mar 1;346 Pt 2:385-91
references.pmid: 10677357
references.citation: Chembiochem. 2008 Jul 21;9(11):1729-34
references.pmid: 18604834
references.citation: J Biol Inorg Chem. 2008 Jan;13(1):35-46
references.pmid: 17874148
references.citation: J Am Chem Soc. 2012 Apr 4;134(13):5798-800
references.pmid: 22420507
references.citation: Cell. 2007 Dec 14;131(6):1047-58
references.pmid: 18083096
references.citation: Biochem Biophys Res Commun. 1989 Dec 15;165(2):838-44
references.pmid: 2512923
references.citation: NMR Biomed. 1994 Nov;7(7):330-8
references.pmid: 7718434
references.citation: Bioorg Med Chem. 2011 Feb 1;19(3):1097-105
references.pmid: 20691598
references.citation: Nat Biotechnol. 2005 Aug;23(8):945-6
references.pmid: 16082363
references.citation: Contrast Media Mol Imaging. 2011 Jul-Aug;6(4):219-28
references.pmid: 21861282
references.citation: Proc Natl Acad Sci U S A. 1987 Aug;84(16):6005-9
references.pmid: 3112778
references.citation: J Am Chem Soc. 2013 Jan 30;135(4):1617-24
references.pmid: 23289583
references.citation: Proc Natl Acad Sci U S A. 1983 Dec;80(23):7178-82
references.pmid: 6417665
references.citation: Angew Chem Int Ed Engl. 2005 Mar 11;44(12):1813-5
references.pmid: 15723362
references.citation: Langmuir. 2008 Jul 15;24(14):7596-8
references.pmid: 18558729
references.citation: Nat Mater. 2013 Mar;12(3):268-75
references.pmid: 23353626
references.citation: Environ Health Perspect. 1990 Mar;84:99-106
references.pmid: 2112459
references.citation: Magn Reson Med. 2013 Sep;70(3):859-64
references.pmid: 23059893
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14707-12
references.pmid: 17003117
references.citation: Chem Sci. 2011 Jun;2(6):1103-1110
references.pmid: 25364495
references.citation: Science. 2006 Oct 20;314(5798):446-9
references.pmid: 17053143
references.citation: NMR Biomed. 2013 Jul;26(7):860-71
references.pmid: 23606473
references.citation: Q Rev Biophys. 1984 Feb;17(1):83-124
references.pmid: 6091170
references.citation: Magn Reson Med. 2011 Apr;65(4):927-48
references.pmid: 21337419
references.citation: J Am Chem Soc. 2010 Feb 17;132(6):1813-5
references.pmid: 20095603
references.citation: NMR Biomed. 2013 Jul;26(7):810-28
references.pmid: 23303716
references.citation: J Neurochem. 1999 Jun;72(6):2617-20
references.pmid: 10349874
references.citation: Chem Soc Rev. 2010 Jan;39(1):51-60
references.pmid: 20023836