title: Environmentally responsive MRI contrast agents.
abstract: Biomedical imaging techniques can provide a vast amount of anatomical information, enabling diagnosis and the monitoring of disease and treatment profile. MRI uniquely offers convenient, non-invasive, high resolution tomographic imaging. A considerable amount of effort has been invested, across several decades, in the design of non toxic paramagnetic contrast agents capable of enhancing positive MRI signal contrast. Recently, focus has shifted towards the development of agents capable of specifically reporting on their local biochemical environment, where a switch in image contrast is triggered by a specific stimulus/biochemical variable. Such an ability would not only strengthen diagnosis but also provide unique disease-specific biochemical insight. This feature article focuses on recent progress in the development of MRI contrast switching with molecular, macromolecular and nanoparticle-based agents.
authors.affiliation: Department of Chemistry, University of Oxford, South Parks Road, Oxford, OX1 3QZ, UK. jason.davis@chem.ox.ac.uk.
authors.forename: Gemma-Louise
authors.initials: GL
authors.lastname: Davies
authors.forename: Iris
authors.initials: I
authors.lastname: Kramberger
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Davis
mesh_terms: D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances / Q000138:chemical synthesis / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D010084:Oxidation-Reduction
chemical_list: D003287:Contrast Media; D046911:Macromolecular Substances; D009942:Organometallic Compounds
references.citation: Magn Reson Med. 1989 Apr;10(1):135-44
references.pmid: 2547135
references.citation: Chem Commun (Camb). 2011 Mar 21;47(11):3144-6
references.pmid: 21270985
references.citation: Curr Mol Med. 2009 May;9(4):442-58
references.pmid: 19519402
references.citation: Magn Reson Imaging. 1999 Jan;17(1):83-9
references.pmid: 9888401
references.citation: Biomaterials. 2011 Sep;32(27):6570-8
references.pmid: 21641639
references.citation: NMR Biomed. 2013 Jul;26(7):872-84
references.pmid: 23225197
references.citation: Chem Soc Rev. 2006 Jun;35(6):512-23
references.pmid: 16729145
references.citation: Magn Reson Med. 1992 Sep;27(1):44-51
references.pmid: 1435209
references.citation: J Control Release. 2012 Jul 20;161(2):307-16
references.pmid: 22580190
references.citation: J Mater Chem. 2012 Oct 16;22(43):22848-22850
references.pmid: 26052183
references.citation: Chem Sci. 2012 Jun 1;3(6):1829-1834
references.pmid: 25431649
references.citation: Int J Nanomedicine. 2008;3(2):201-10
references.pmid: 18686779
references.citation: Nature. 2008 Jun 12;453(7197):869-78
references.pmid: 18548064
references.citation: J Inorg Biochem. 2008 May-Jun;102(5-6):1112-9
references.pmid: 18329102
references.citation: MAGMA. 2005 Sep;18(4):186-92
references.pmid: 16155762
references.citation: J Am Chem Soc. 2008 Jan 30;130(4):1376-83
references.pmid: 18179213
references.citation: Chem Commun (Camb). 2012 Sep 25;48(74):9290-2
references.pmid: 22875137
references.citation: Chemistry. 2001 Feb 2;7(3):600-10
references.pmid: 11261657
references.citation: Biomacromolecules. 2012 Nov 12;13(11):3877-86
references.pmid: 23013152
references.citation: Chem Commun (Camb). 2009 Mar 14;(10):1246-8
references.pmid: 19240888
references.citation: Chembiochem. 2008 Jul 21;9(11):1729-34
references.pmid: 18604834
references.citation: Nanomedicine. 2011 Dec;7(6):1001-8
references.pmid: 21515406
references.citation: Angew Chem Int Ed Engl. 2008;47(45):8568-80
references.pmid: 18825758
references.citation: Sci Rep. 2013;3:1024
references.pmid: 23289066
references.citation: Nat Nanotechnol. 2010 Nov;5(11):815-21
references.pmid: 20972435
references.citation: Biomaterials. 2013 Jan;34(2):492-500
references.pmid: 23059004
references.citation: J Am Chem Soc. 2008 Apr 2;130(13):4214-5
references.pmid: 18331033
references.citation: J Am Chem Soc. 2009 Jun 24;131(24):8527-36
references.pmid: 19489557
references.citation: Angew Chem Int Ed Engl. 2000 Feb;39(4):747-750
references.pmid: 10760856
references.citation: J Am Chem Soc. 2009 Aug 19;131(32):11387-91
references.pmid: 19630391
references.citation: Inorg Chem. 1999 Mar 8;38(5):1002-1005
references.pmid: 11670874
references.citation: Magn Reson Imaging. 1985;3(1):11-6
references.pmid: 3923289
references.citation: Dalton Trans. 2011 Jan 14;40(2):484-8
references.pmid: 21113542
references.citation: Bioorg Med Chem. 2012 Jan 15;20(2):769-74
references.pmid: 22206870
references.citation: Mol Cell Biol. 1987 Feb;7(2):725-37
references.pmid: 3821727
references.citation: Nat Biotechnol. 2000 Mar;18(3):321-5
references.pmid: 10700150
references.citation: Magn Reson Med. 2000 Nov;44(5):799-802
references.pmid: 11064415
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 8;108(45):18400-5
references.pmid: 22025712
references.citation: Nano Lett. 2008 Feb;8(2):415-9
references.pmid: 18215084
references.citation: Nat Rev Neurosci. 2005 Jun;6(6):449-62
references.pmid: 15891778
references.citation: Inorg Chem. 2007 Jun 25;46(13):5260-70
references.pmid: 17539632
references.citation: Chemistry. 2010 Sep 17;16(35):10727-34
references.pmid: 20669190
references.citation: Adv Drug Deliv Rev. 2006 Dec 30;58(15):1655-70
references.pmid: 17125884
references.citation: Chem Commun (Camb). 2007 Oct 21;(39):4044-6
references.pmid: 17912410
references.citation: J Control Release. 2013 Feb 28;166(1):22-9
references.pmid: 23246469
references.citation: Chem Rev. 1999 Sep 8;99(9):2293-352
references.pmid: 11749483
references.citation: Angew Chem Int Ed Engl. 2010 Mar 22;49(13):2382-4
references.pmid: 20191650
references.citation: Chemistry. 2005 May 6;11(10):3064-76
references.pmid: 15776490
references.citation: Contrast Media Mol Imaging. 2010 Sep-Oct;5(5):294-6
references.pmid: 20973114
references.citation: Chem Commun (Camb). 2003 Oct 21;(20):2574-5
references.pmid: 14594287
references.citation: Mol Pharm. 2012 Jul 2;9(7):1911-8
references.pmid: 22657107
references.citation: Chem Soc Rev. 2006 Jun;35(6):557-71
references.pmid: 16729149
references.citation: Chemistry. 2006 Jan 23;12(4):989-1003
references.pmid: 16311990
references.citation: Bioconjug Chem. 1991 Nov-Dec;2(6):394-7
references.pmid: 1805934
references.citation: Inorg Chem. 2012 Jan 2;51(1):170-8
references.pmid: 22128872
references.citation: Dalton Trans. 2011 Jun 21;40(23):6087-103
references.pmid: 21409202
references.citation: Science. 2008 Oct 17;322(5900):421-4
references.pmid: 18927389
references.citation: J Am Chem Soc. 2005 Sep 21;127(37):12847-55
references.pmid: 16159278
references.citation: Contrast Media Mol Imaging. 2006 Nov-Dec;1(6):267-78
references.pmid: 17191767
references.citation: Chem Rev. 2010 May 12;110(5):2960-3018
references.pmid: 20397688
references.citation: J Med Chem. 2013 Mar 28;56(6):2466-77
references.pmid: 23469759
references.citation: Z Naturforsch C J Biosci. 2006 Jan-Feb;61(1-2):74-80
references.pmid: 16610221
references.citation: Inorg Chem. 2008 Nov 17;47(22):10788-95
references.pmid: 18928280
references.citation: Inorg Chem. 2007 Aug 6;46(16):6632-9
references.pmid: 17625839
references.citation: Biomacromolecules. 2009 Feb 9;10(2):374-81
references.pmid: 19128056
references.citation: J Control Release. 2010 Apr 2;143(1):120-7
references.pmid: 19969035
references.citation: Ann Biomed Eng. 2011 Apr;39(4):1335-48
references.pmid: 21331662
references.citation: Magn Reson Med. 2006 Feb;55(2):309-15
references.pmid: 16402385
references.citation: Dalton Trans. 2010 Apr 14;39(14):3407-11
references.pmid: 20379534
references.citation: J Am Chem Soc. 2001 Aug 8;123(31):7601-9
references.pmid: 11480981
references.citation: J Am Chem Soc. 2008 Feb 20;130(7):2154-5
references.pmid: 18217764
references.citation: Acc Chem Res. 2009 Jul 21;42(7):948-57
references.pmid: 19265438
references.citation: J Biol Inorg Chem. 2002 Sep;7(7-8):757-69
references.pmid: 12203012
references.citation: Chem Commun (Camb). 2011 May 7;47(17):4998-5000
references.pmid: 21424019
references.citation: J Control Release. 2012 Jul 20;161(2):317-27
references.pmid: 22565055
references.citation: Org Biomol Chem. 2013 Feb 28;11(8):1294-305
references.pmid: 23223612
references.citation: J Am Chem Soc. 2010 Jun 16;132(23):7836-7
references.pmid: 20481537
references.citation: Dalton Trans. 2011 May 14;40(18):5018-25
references.pmid: 21451883
references.citation: J Magn Reson Imaging. 2009 Dec;30(6):1259-67
references.pmid: 19938038
references.citation: Chem Commun (Camb). 2007 Apr 7;(13):1331-3
references.pmid: 17377672
references.citation: J Cereb Blood Flow Metab. 2008 Jun;28(6):1165-74
references.pmid: 18270519
references.citation: Inorg Chem. 2008 Feb 18;47(4):1370-81
references.pmid: 18166011
references.citation: J Control Release. 2006 May 30;112(3):350-6
references.pmid: 16631270
references.citation: Chembiochem. 2010 Apr 12;11(6):785-7
references.pmid: 20209557
references.citation: Chem Commun (Camb). 2013 Apr 7;49(27):2732-46
references.pmid: 23392443
references.citation: Medchemcomm. 2012 Apr 1;3(4):480-483
references.pmid: 24013159
references.citation: Inorg Chem. 2012 Jul 2;51(13):7210-7
references.pmid: 22716284
references.citation: J Pharm Pharm Sci. 2012;15(4):592-605
references.pmid: 23106961
references.citation: Chemistry. 2008;14(24):7250-8
references.pmid: 18601236
references.citation: Angew Chem Int Ed Engl. 1999 Nov 2;38(21):3192-3194
references.pmid: 10556899
references.citation: Radiother Oncol. 1984 Dec;2(4):343-66
references.pmid: 6097949
references.citation: Acc Chem Res. 2009 Jul 21;42(7):893-903
references.pmid: 19537782
references.citation: Chemistry. 2002 Nov 15;8(22):5121-31
references.pmid: 12613030
references.citation: Chem Commun (Camb). 2009 Oct 28;(40):6044-6
references.pmid: 19809638
references.citation: J Control Release. 2012 Feb 10;157(3):478-84
references.pmid: 21939700
references.citation: J Am Chem Soc. 2002 Apr 10;124(14):3514-5
references.pmid: 11929234
references.citation: Int J Pharm. 2004 Apr 15;274(1-2):75-83
references.pmid: 15072784
references.citation: Chemistry. 2011 Feb 1;17(5):1529-37
references.pmid: 21268155
references.citation: Angew Chem Int Ed Engl. 2001 Aug 3;40(15):2903-2906
references.pmid: 11500904
references.citation: Chem Commun (Camb). 2011 Feb 7;47(5):1539-41
references.pmid: 21103497
references.citation: Chem Rev. 2010 May 12;110(5):2921-59
references.pmid: 20067234
references.citation: Angew Chem Int Ed Engl. 2011 Nov 4;50(45):10589-93
references.pmid: 21928456
references.citation: Biomaterials. 2013 Jun;34(17):4387-93
references.pmid: 23478033
references.citation: J Am Chem Soc. 2006 Dec 20;128(50):15942-3
references.pmid: 17165700
references.citation: Angew Chem Int Ed Engl. 2011 Jul 4;50(28):6283-6
references.pmid: 21618367
references.citation: Chemphyschem. 2011 Mar 14;12(4):772-6
references.pmid: 21387521
references.citation: Contrast Media Mol Imaging. 2012 Nov-Dec;7(6):501-8
references.pmid: 22991316
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18584-9
references.pmid: 19011099
references.citation: J Am Chem Soc. 2008 Feb 27;130(8):2546-52
references.pmid: 18247608
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):13881-6
references.pmid: 17724345
references.citation: J Am Chem Soc. 2005 Jan 19;127(2):799-805
references.pmid: 15643906
references.citation: ACS Nano. 2013 Jan 22;7(1):330-8
references.pmid: 23199030
references.citation: Chem Biol. 2002 Sep;9(9):1027-32
references.pmid: 12323377
references.citation: Chem Rev. 2010 May 12;110(5):3043-59
references.pmid: 20384323
references.citation: J Am Chem Soc. 2004 Aug 4;126(30):9248-56
references.pmid: 15281814
references.citation: J Pharm Pharmacol. 2008 Aug;60(8):1049-60
references.pmid: 18644197
references.citation: Angew Chem Int Ed Engl. 2009;48(35):6547-51
references.pmid: 19630041
references.citation: Chem Commun (Camb). 2012 Feb 28;48(18):2436-8
references.pmid: 22273600
references.citation: Inorg Chem. 2006 Jun 26;45(13):5092-102
references.pmid: 16780331
references.citation: Chemistry. 2003 Mar 17;9(6):1394-404
references.pmid: 12645029
references.citation: J Magn Reson Imaging. 1995 Nov-Dec;5(6):719-24
references.pmid: 8748492
references.citation: Chem Commun (Camb). 2009 Jul 14;(26):3922-4
references.pmid: 19662253
references.citation: Chem Commun (Camb). 2002 Oct 21;(20):2366-7
references.pmid: 12430443
references.citation: Biomaterials. 2012 Oct;33(29):7126-37
references.pmid: 22789722
references.citation: J Am Chem Soc. 2006 Sep 6;128(35):11326-7
references.pmid: 16939235
references.citation: J Magn Reson Imaging. 1993 Jan-Feb;3(1):157-65
references.pmid: 8428083
references.citation: Tetrahedron. 2009 Feb;65(7):1241
references.pmid: 20126289
references.citation: Angew Chem Int Ed Engl. 2013 Apr 2;52(14):3926-30
references.pmid: 23450786
references.citation: IEEE Eng Med Biol Mag. 2004 Sep-Oct;23(5):57-64
references.pmid: 15565800
references.citation: Anal Biochem. 1995 Jul 1;228(2):312-7
references.pmid: 8572312
references.citation: J Am Chem Soc. 2002 Mar 27;124(12):3152-62
references.pmid: 11902904
references.citation: J Magn Reson. 2000 Mar;143(1):79-87
references.pmid: 10698648
references.citation: Angew Chem Int Ed Engl. 2005 Oct 21;44(41):6766-9
references.pmid: 16173108
references.citation: Magn Reson Med. 2006 Jun;55(6):1272-80
references.pmid: 16700014
references.citation: Analyst. 2007 Nov;132(11):1153-60
references.pmid: 17955150
references.citation: Chem Commun (Camb). 2013 Jan 4;49(1):60-2
references.pmid: 23164954