Abstract
This chapter is devoted to survey the major classes of MRI contrast agent (CA), their modes of action, and some of the most significative applications. The two more established classes of MRI CA are represented by paramagnetic metal complexes (i.e., Gd(III) and Mn(II)) and iron oxide particles, acting on T1 and T2* of the water protons signals, respectively. Along the years, many efforts have been devoted to endow these relaxation enhancement agents with improved sensitivity, targeting, and responsive properties that have markedly broadened the range of applications in respect to the clinically used systems. CEST agents represent innovative frequency-encoding probes that yield negative contrast in the MR images upon transfer of saturated magnetization from the agent to the “bulk” water signal. Interesting developments have been attained that markedly increase the number and typology of systems with CEST properties. Currently, much attention is devoted to hyperpolarized molecules that display a sensitivity enhancement sufficient for their direct exploitation for the formation of the MR image. A real breakthrough is provided by the use of molecules (such as pyruvate) that report about the cellular metabolism thanks to the maintainment of the hyperpolarization in the derived species. Finally, 19F-containing molecules have been considered as the improved sensitivity of the new MRI scanner generation makes it possible to acquire images based on this heteronucleous.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Adams RW, Aguilar JA, Atkinson KD, Cowley MJ, Elliott PIP, Duckett SB, Green GGR, Khazal IG, López-Serrano J, Williamson DC (2009) Science 323:1708–1711
Aime S, Ascenzi P, Comoglio E et al (1995) J Am Chem Soc 117:9365
Aime S, Botta M, Fasano M, Geninatti Crich S, Terreno E (1996) J Biol Inorg Chem 1:312–319
Aime S, Botta M, Fasano M, Terreno E (1998) Chem Soc Rev 27:19
Aime S, Chiaussa M, Digilio G et al (1999a) J Biol Inorg Chem 4:766–774
Aime S, Botta M, Geninatti S et al (1999b) Chem Comm 1577 -1578
Aime S, Gianolio E, Terreno E et al (2000) J Biol Inorg Chem 5:488
Aime S, Fasano M, Terreno E, Botta M (2001) In: Merbach AE, Tóth E (eds) The chemistry of contrast agents in medical magnetic resonance imaging. Wiley, Chichester
Aime S, Cabella C, Colombatto S, Geninatti Crich S, Gianolio E, Maggioni F (2002a) JMRI 16:394–406
Aime S, Barge A, Delli Castelli D, Fedeli F, Mortillaro A, Nielsen FU, Terreno E (2002b) Magn Reson Med 47: 639
Aime S, Delli Castelli D, Terreno E (2003a) Angew Chemie Int Ed 42:4527
Aime S, Gobetto R, Reineri F (2003b) J Chem Phys 119:8890–8897
Aime S, Delli Castelli D, Terreno E (2005) Angew Chem Int Ed 44:5513–5515
Aime S, Delli Castelli D, Lawson D, Terreno E (2007) J Am Chem Soc 129:2430–2431
Aime S, Dastrù W, Giovenzana GB, Gobetto R, Reineri F, Santelia D, Viale A (2008) J Am Chem Soc 130:15047–15053
Albers MJ, Bok R, Chen AP, Cunningham CH, Zierhut ML, Zhang VY, Kohler SJ, Tropp J, Hurd R, Yen Y-F et al (2008) Cancer Res 68:8607–8615
Albert MS, Cates GD, Driehuys B, Happer W, Saam B, Springer CS Jr et al (1994) Nature 370:199–201
Altes TA, Salerno M (2004) J Thoracic Imag 19:250–258
Anelli PL, Bertini I, Fragai M et al (2000) Eur J Inorg Chem: 625–630
Ardenkjaer-Larsen JH, Fridlund B, Gram A, Hansson G, Hansson L, Lerche MH, Servin R, Thaning M, Golman K (2003) Proc Natl Acad Sci USA 100: 10158–10163
Artemov D, Mori N, Ravi R, Bhujwalla ZM (2003) Cancer Res 63:2723–2727
Babincova M, Altanerova V, Lambert M, Altaner C, Machova E, Sramka M, Babinec P (2000) Naturforsch C 55:278
Babincova M, Leszczynska D, Sourivong P, Babinec P, Leszczynski J (2004) Med Hypotheses 62:375
Banci L, Bestini I, Luchinat C (1991) Nuclear and electronic relaxation. VCH, Weinheim
Bargon J, Natterer J (1997) Progr Nucl Magn Reson Spect 31:293–315
Barkemeyer J, Haake M, Bargon J (1995) J Am Chem Soc 117:2927–2928
Bhattacharya P et al (2009) Abstract n. 461, 50th Experimental Nuclear Magnetic Resonance Conference, Pacific Grove, California, March 29–April 3
Bogdanov A, Matuszewski L, Bremer C, Petrovski A, Weissleder R (2002) Mol Imaging 1:16–23
Botta M (2000) Eur J Inorg Chem 3:399
Brücher E, Sherry AD (2001) In: Merbach AE, Tóth E (eds) The chemistry of contrast agents in medical magnetic resonance imaging. Wiley, Chichester
Bulte JW, De Cuyper M (2003) Methods Enzymol 373:175
Bulte JW, De Cuyper M, Despres D, Franck JA (1999) J Magn Reson Imaging 9:329
Callot V, Canet E, Brochot J, Viallon M, Humblot H, Briguet A, Tournier H, Cremillieux Y (2001) Magn Res Med 46: 535–540
Carter D, Ho JX (1994) Adv Prot Chem 45:153–203
Chekmenev EY, Hovener J, Norton VA, Harris K, Batchelder LS, Bhattacharya P, Ross BD, Weitekamp DP (2008) J Am Chem Soc 130:4212–4213
Chen AP, Kurhanewicz J, Bok R, Xu D, Joun D, Zhang V, Nelson SJ, Hurd RE, Vigneron DB (2008) Magn Res Imag 26:721–726
Comment A, van den Brandt B, Uffmann K, Kurdzesau F, Jannin S, Konter JA, Hautle P, Wenckebach WTh, Gruetter R, van der Klink JJ (2007) Conc Magn Reson Part B 31B: 255–269
Corot C, Robert P, Idee JM, Port M (2006) Adv Drug Deliv Rev 58:471
Cunningham CH, Arai T, Yang PC, McConnell MV, Pauly JM, Conolly SM (2005) Magn Reson Med 53:999–1005
Day SE, Kettunen MI, Gallagher FA, Hu D-E, Lerche M, Wolber J, Golman K, Ardenkjaer-Larsen JH, Brindle KM (2007) Nat Med 13:1382–1387
Delli Castelli D, Terreno E, Carrera C, Giovenzana GB, Mazzon R, Rollet S, Visigalli M, Aime S (2008) Inorg Chem 47:2928–2930
Dousset V, Brochet B, Deloire MSA, Lagoarde L, Barroso B, Caille JM, Petri KG (2006) Am J Neuroradiol 27:1000
Duckett SB, Wood NJ (2008) Coordination Chem Rev 252:2278–2291
Engberink RDO, van der Pol SMA, Döpp ED, de Vries HE, Blezer ELA (2007) Radiology 243:467–474
Engelstadt BL, Wolf GL (1988) In: Stark DD, Bradley WG Jr (eds) Magnetic Resonance Imaging. V.C. Mosby, St. Louis
Fan X, River JN, Zamora M, Al-Hallaq HA, Karczmar GS (2002) Int J Radiat Oncol Biol Phys 54:1202–1209
Fortin-Ripoche JP, Martina MS, Gazeau F, Menager C, Wilhelm C, Bacri JC, Lesieur S, Clement O (2006) Radiology 239:415
Fossheim S, Kellar KE, Fahlvik AK, Klaveness J (1997) Magn Reson Imaging 15:193-202
Frangioni JV, Hajjar RJ (2004) Circulation 110:3378–3383
Gabellieri C, Reynolds S, Lavie A, Payne GS, Leach MO, Eykyn TR (2008) J Am Chem Soc 130:4598–4599
Gallagher FA, Kettunen MI, Day SE, Lerche M, Brindle KM (2008a) Magn Res Med 60:253–257
Gallagher FA, Kettunen MI, Day SE, Hu D-E, Ardenkjær-Larsen JH, Zandt R, Jensen PR, Karlsson M, Golman K, Lerche MH, Brindle KM (2008b) Nature 453:940–943
Gianolio E, Giovenzana GB, Longo D, Longo I, Menegotto I, Aime S (2007) Chem Eur J 13:5785–5797
Glogard C, Stensrud G, Aime S (2003) Magn Res Chem 41:585
Goffeney N, Bulte JWM, Duyn J, Bryant LH Jr, van Zijl PCM (2001) J Am Chem Soc 123:8628
Goldman M, Johannesson H (2005) CR Phisique 6:575–581
Goldman M, Johannesson H, Axelsson O, Karlsson M (2005) Magn Res Imag 23:153–157
Golman K, Axelsson O, Johannesson H, Månsson S, Olofsson C, Petersson JS (2001) Magn Reson Med 46:1–5
Golman K, Zandt R, Lerche M, Perhson R, Ardenkjaer-Larsen H (2006) Cancer Res 66:10855–10860
Hall DA, Maus DC, Gerfen GJ, Inati SJ, Becerra LR, Dahlquist FW, Griffin RG (1997) Science 276:930–932
Henkelman RM, Stanisz GJ, Graham SJ (2001) NMR Biomed 14:57–64
Hu JZ, Solum MS, Wind RA, Nilsson BL, Peterson MA, Pugmire RJ, Grant DM (2000) J Phys Chem A 104:4413–4420
Hunjan S, Zhao D, Canstandtinescu A, Hahan EW, Antich PP, Mason RP (2001) Int J Radiat Oncol Biol Phys 49:1097–1108
Ishii M, Emami K, Kadlecek S, Petersson JS, Golman K, Vahdat V, Yu J, Cadman RV, MacDuffie-Woodburn J, Stephen M et al (2007) Magn Res Med 57:459–463
Ito A, Shinkai M, Honda H, Kobayashi T (2005) J Biosci Bioeng 100:1
Johannesson H, Axelsson O, Karlsson M (2004) CR Physique 5:315–324
Johansson E, Mansson, S, Wirestam R, Svensson J, Petersson JS, Golman K, Stahlberg F (2004) Magn Reson Med 51: 464–472
Kircher MF, Allport JR, Graves EE, Love V, Josephson L, Lichtman AH, Weissleder R (2003) Cancer Res 63:6838–6846
Larson PEZ, Kerr AB, Chen AP, Lustig MS, Zierhut ML, Hu S, Cunningham CH, Pauly JM, Kurhanewicz J, Vigneron DB (2008) J Magn Res 194:121–127
Lauffer R, Mc Murry TJ, Dunham SO et al (1997) PCT Int Appl WO9736619
Lauffer R, Parmelee D, Dunham S et al (1998) Radiology 207:529–538
Levin YS, Mayer D, Yen Y-F, Hurd RE, Spielman DM (2007) Magn Res Med 58:245–252
Lowe MP, Parker D, Reany O et al (2001) J Am Chem Soc 123:7601
Magnusson P, Johansson E, Månsson S, Petersson JS, Chai C-M, Hansson G, Axelsson O, Golman K (2007) Magn Res Med 57:1140–1147
Mansson S, Johansson E, Magnusson P, Chai C-M, Hansson G, Petersson JS, Stahlberg F, Golman K (2006) 13C imaging – a new diagnostic platform. Eur Radiol 16:57–67
Martina MS, Fortin JP, Menager C, Clement O, Barratt G, Grabielle-Madelmont C, Gazeau F, Cabuil V, Lesieur S (2005) J Am Chem Soc 127:10676
Merritt ME, Harrison C, Kovacs Z, Kshirsagar P, Malloy CR, Sherry AD (2007a) J Am Chem Soc 129:12942–12943
Merritt ME, Harrison C, Storey C, Jeffrey FM, SherryAD MCR (2007b) Proc Natl Acad Sci USA 104:19773–19777
Moller HE, Chen XJ, Saam B, Hagspiel KD, Johnson GA, Altes TA, de Lange EE, Kauczor HU (2002) Magn Res Med 47:1029–1051
Morawski AM, Winter PM, Yu X, Fuhrhop RW, Scott MJ, Hockett F, Robertson JD, Gaffney PJ, Lanza GM, Wickline SA (2004) Magn Reson Med 52:1255–1262
Mulder WJM, Castermans K, van Beijnum JR, oude Egbrink MGA, Chin PTK, Fayad ZA, Löwik CWJM, Kaijzel EL, Que I, Storm G, Strijkers GJ, Griffioen AW, Nicolay K (2009) Angiogenesis 12:17–24
Muller RN, Vander Elst L, Roch A, Peters JA, Csajbok E, Gillis P, Gossuin Y (2005) Adv Inorg Chem 57:239
Neubauer AM, Myerson J, Caruthers SD, Hockett FD, Winter PM, Chen J, Gaffney PJ, Robertson JD, Lanza GM, Wickline SA (2008) Magn Reson Med 60:1066–1072
Nivorozhkin AL, Kolodziej AF, Caravan P et al (2001) Angew Chemie Int Ed 40:2903
Norek M, Kampert E, Zeitler U, Peters JA (2008) J Am Chem Soc 130:5335–5340
Noth U, Grohn P, Jork A, Zimmermann U, Haase A, Lutz J (1999) Magn Reson Med 42:1039–1047
Partlow KC, Chen J, Brant JA, Neubauer AM, Meyerrose TE, Creer MH, Nolta JA, Caruthers SD, Lanza M, Wickline SA (2007) FASEB J 21:1647–1654
Pikkemaat JA, Wegh RT, Lamerichs R, van de Molengraaf RA, Langereis S, Burdinski D, Raymond AY, Janssen HM, de Waal BF, Willard NP, Meijer EW, Grull H (2007) Contrast Media Mol Imaging 2:229–239
Raghunand N, Howison C, Sherry AD et al (2003) Magn Reson Med 49:249
Rinck PA (1993) Magnetic resonance in medicine. Blackwell, Oxford
Rinck PA (2003) Magnetic resonance in medicine. ABW Wissenschaftsverlag GmbH, Berlin
Rosen BR, Belliveau JW, Aronen HJ, Kennedy D, Buchbinder BR, Fischman A, Gruber M, Glas J, Weisskoff RM, Cohen MS, Hochberg FH, Brady TJ (1991) Magn Reson Med 22:293
Rummeny EJ (1997) Marchal Acta Radiol 38:626
Saleh A, Schroeter M, Jonkmanns C, Hartung HP, Modder H, Jander S (2004) Brain 127:1670
Schlemmer HP, Becker M, Bachert P, Dietz A, Rudat V, Vanselow B, Wollensack P, Zuna I, Knopp MV, Weidauer H, Wannenmacher M, van Kaick G (1999) Cancer Res 59:2363–2369
Schmitt-Willich H, Brehm M, Evers CLJ et al (1999) Inorg Chem 38:1134
Schroder L, Lowery TJ, Hilty C, Wemmer DE, Pines A (2006) Science 314:446–449
Schroeder MA, Cochlin LE, Heather LC, Clarke K, Radda GK, Tyler DJ (2008) Proc Natl Acad Sci USA 105:12051–12056
Schroeder MA, Atherton EJ, Cochlin LE, Clarke K, Radda GK, Tyler DJ (2009) Magn Res Med 61:1007–1014
Schumann Giamperi G (1993) Invest Radiol 28:753
Sipkins DA, Cheresh DA, Kazemi MR, Nevin LM, Bednarski MD, Li KCP (1998) Nat Med 4:623–626
Spence MM, Rubin SM, Dimitrov IE, Ruiz EJ, Wemmer DE, Pines A, Yaoi SO, Tiani F, Schultzi PG (2001) Proc Natl Acad Sci USA 98:10654–10657
Srinivas M, Morel PA, Ernst LA, Laidlaw DH, Ahrens ET (2007) Magn Reson Med 58:725–734
Swanson SD, Rosen MS, Agranoff BW, Coulter KP, Welsh RC, Chupp TE (1997) Magn Reson Med 38:695–698
Terreno E, Delli Castelli D, Cravotto G, Milone L, Aime S (2004) Invest Radiol 39:235–243
Terreno E, Cabella C, Carrera C, Delli Castelli D, Lanzardo S, Mazzon R, Rollet S, Visigalli M, Aime S (2007a), Proc Joint Annual Meeting ISMRM-ESMRMB, Berlin, Germany, p. 248
Terreno E, Cabella C, Carrera C, Delli Castelli D, Mazzon R, Rollet S, Stancanello J, Visigalli M, Aime S (2007b) Angew Chem Int Ed 46:966–968
Terreno E, Sanino A, Carrera C, Delli Castelli D, Giovenzana GB, Lombardi A, Mazzon R, Milone L, Visigalli M, Aime S (2008a) J Inorg Biochem 102:1112–1119
Terreno E, Barge A, Beltrami L, Cravotto G, Delli Castelli D, Fedeli F, Jebasingh B, Aime S (2008b) Chem Commun 7:600–602
Terreno E, Delli Castelli D, Milone L, Rollet S, Stancanello J, Violante E, Aime S (2008c) Contrast Media Mol Imaging 3:38–43
Tweedle MF (1989) In: Bünzli JCG, Choppin GR (eds) Lanthanide probes in life, chemical and earth sciences: theory and practice. Amsterdam, Elsevier
Uggeri F, Aime S, Anelli PL et al (1995) Inorg Chem 34:633
Vasalatiy O, Gerard RD, Zhao P, Sun X, Sherry AD (2008) Bioconjug Chem 19:598–606
Ward KM, Balaban RS (2000) Magn Reson Med 44:799–802
Ward KM, Aletras AH, Balaban RS (2000) J Magn Res 143:79
Weinmann HJ, Mühler A, Radüchel B (2000) In: Young IR (ed) Biomedical magnetic resonance imaging and spectroscopy. Wiley, Chichester
Weissleder R, Mahmood U (2001) Radiology 219:316–333
Winter PM, Caruthers SD, Kassner A, Harris TD, Chinen LK, Allen JS, Lacy EK, Zhang HY, Robertson JD, Wickline SA, Lanza GM (2003) Cancer Res 63:5838
Winter PM, Cai K, Chen J, Adair CR, Kiefer GE, Athey PS, Gaffney PJ, Buff CE, Robertson JD, Caruthers SD, Wickline SA, Lanza GM (2006) Magn Reson Med 56:1384–1388
Woessner DE, Zhang S, Merritt ME, Sherry AD (2005) Magn Res Med 53:790
Wolber J, Rowland IJ, Leach MO, Bifone A (1999) Magn Reson Med 41:442–449
Wolber J, Cherubini A, Leach MO, Bifone A (2000) Magn Reson Med 43:491–496
Woods M, Woessner DE, Zhao P, Pasha A, Yang MY, Huang CH, Vasalitiy O, Morrow JR, Sherry AD (2006) J Am Chem Soc 128:10155–10162
Zandt R et al (2009) Abstracts n. 4380 and 4381, 17th ISMRM Scientific Meeting & Exhibition, Honolulu, Hawaii (USA), April 18–24
Zhang SR, Wu KC, Sherry AD (1999) Angew Chemie Int Ed 38:3192
Zhang S, Winter P, Wu K, Sherry AD (2001) J Am Chem Soc 123:1517–1518
Zhang ZD, Greenfield M, Spiller TJ, McMurry RB, Lauffer RB, Caravan P (2005) Angewandte Chemie Int Ed 44:6766
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Gianolio, E., Viale, A., Castelli, D.D., Aime, S. (2011). MR Contrast Agents. In: Kiessling, F., Pichler, B. (eds) Small Animal Imaging. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-12945-2_13
Download citation
DOI: https://doi.org/10.1007/978-3-642-12945-2_13
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-12944-5
Online ISBN: 978-3-642-12945-2
eBook Packages: MedicineMedicine (R0)