, Volume 21, Issue 4, pp 469–490 | Cite as

Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review

  • Marc PortEmail author
  • Jean-Marc Idée
  • Christelle Medina
  • Caroline Robic
  • Monique Sabatou
  • Claire Corot


Gadolinium-based contrast agents are widely used to enhance image contrast in magnetic resonance imaging (MRI) procedures. Over recent years, there has been a renewed interest in the physicochemical properties of gadolinium chelates used as contrast agents for MRI procedures, as it has been suggested that dechelation of these molecules could be involved in the mechanism of a recently described disease, namely nephrogenic systemic fibrosis (NSF). The aim of this paper is to discuss the structure-physicochemical properties relationships of marketed gadolinium chelates in regards to their biological consequences. Marketed gadolinium chelates can be classified according to key molecular design parameters: (a) nature of the chelating moiety: macrocyclic molecules in which Gd3+ is caged in the pre-organized cavity of the ligand, or linear open-chain molecules, (b) ionicity: the ionicity of the complex varies from neutral to tri-anionic agents, and (c) the presence or absence of an aromatic lipophilic residue responsible for protein binding. All these molecular characteristics have a profound impact on the physicochemical characteristics of the pharmaceutical solution such as osmolality, viscosity but also on their efficiency in relaxing water protons (relaxivity) and their biodistribution. These key molecular parameters can also explain why gadolinium chelates differ in terms of their thermodynamic stability constants and kinetic stability, as demonstrated by numerous in vitro and in vivo studies, resulting in various formulations of pharmaceutical solutions of marketed contrast agents. The concept of kinetic and thermodynamic stability is critically discussed as it remains a somewhat controversial topic, especially in predicting the amount of free gadolinium which may result from dechelation of chelates in physiological or pathological situations. A high kinetic stability provided by the macrocyclic structure combined with a high thermodynamic stability (reinforced by ionicity for macrocyclic chelates) will minimize the amount of free gadolinium released in tissue parenchymas.


Magnetic resonance imaging Contrast agents Gadolinium Osmolality Viscosity Relaxivity Thermodynamic stability Kinetic stability Nephrogenic systemic fibrosis 



The authors thank Prof. R.N. Muller and his group for the experimental data shown in Fig. 2 concerning Gd-BT-DO3A, Gd-DTPA, Gd-BOPTA.


  1. Adzamli K, Periasamy MP, Spiller M, Koenig SH (1999) NMRD assessment of Gd-DTPA-bis(methoxyethylamide), (Gd-DTPA-BMEA), a nonionic MRI agent. Invest Radiol 34:410–414PubMedCrossRefGoogle Scholar
  2. Bellin MF, Vasile M, Morel-Precetti S (2003) Currently used non-specific extracellular MR contrast media. Eur Radiol 13:2688–2698PubMedCrossRefGoogle Scholar
  3. Benmelouka M, Van Tol J, Borel A, Port M, Helm L, Brunel LC, Merbach AE (2006) A high-frequency EPR study of frozen solutions of Gd(III) complexes: straightforward determination of the zero-field splitting parameters and simulation of the NMRD profiles. J Am Chem Soc 128:7807–7816PubMedCrossRefGoogle Scholar
  4. Bianchi A, Calabi L, Foresti M, Losi P, Palaeri L, Rodriguez A, Valtancoli B (1999) Interaction of ATP with a Gd3+ complex employed as paramagnetic contrast agent in NMR imaging. Inorganica Chim Acta 288:244–248CrossRefGoogle Scholar
  5. Bianchi A, Calabi L, Giorgi C, Losi P, Mariani P, Paoli P, Rossi P, Valtancoli B, Virtuani M (2000) Thermodynamic and structural properties of Gd3+ complexes with functionalized macrocyclic ligands based upon 1,4,7,10-tetraazacyclododecane. J Chem Soc Dalton Trans 697–705Google Scholar
  6. Bousquet JC, Saini S, Stark DD, Hahn PF, Nigam M, Wittenberg J, Ferrucci JT (1988) Gd-DOTA: characterization of a new paramagnetic complex. Radiology 166:693–698PubMedGoogle Scholar
  7. Broome DR, Cottrell AC, Kanal E (2007) Response to “Will dialysis prevent the development of nephrogenic systemic fibrosis after gadolinium-based contrast administration?”. Am J Roentgenol 189:W234–W235CrossRefGoogle Scholar
  8. Brücher E (2002) Kinetic stability of gadolinium (III) chelates used as MRI contrast agents. Top Curr Chem 221:103–122CrossRefGoogle Scholar
  9. Brücher E, Sherry AD (2001) Stability and toxicity of contrast agents. In: Merbach AE, Toth E (eds) The chemistry of contrast agents in medical magnetic resonance imaging. Wiley, New YorkGoogle Scholar
  10. Bussi S, Fouillet X, Morisetti A (2007) Toxicological assessment of gadolinium release from contrast media. Exp Toxicol Pathol 58:323–330PubMedCrossRefGoogle Scholar
  11. Cacheris WP, Quay SC, Rocklage SM (1990) The relationship between thermodynamics and the toxicity of gadolinium complexes. Magn Reson Imaging 8:467–481PubMedCrossRefGoogle Scholar
  12. Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Gadolinium(III) chelates as MRI contrast agents: structure, dynamics, and applications. Chem Rev 99:2293–2352PubMedCrossRefGoogle Scholar
  13. Caravan P, Comuzzi C, Crooks W, McMurry TJ, Choppin GR, Woulfe SR (2001) Thermodynamic stability and kinetic inertness of MS325, a new blood pool agent for magnetic resonance imaging. Inorg Chem 40:2170–2176PubMedCrossRefGoogle Scholar
  14. Caravan P, Cloutier NJ, Greenfield MT, McDermid SA, Dunham SU, Bulte JW, Amedio JC, Looby RJ, Supkowski RM, Horrocks WD, McMurry TJ, Lauffer RB (2002) The interaction of MS-325 with human serum albumin and its effect on proton relaxation rates. J Am Chem Soc 27;124:3152–3162CrossRefGoogle Scholar
  15. Cavagna FM, Maggioni F, Castelli PM, Dapra M, Imperatori LG, Lorusso V, Jenkins BG (1997) Gadolinium chelates with weak binding to serum proteins. A new class of high-efficiency, general purpose contrast agents for magnetic resonance imaging. Invest Radiol 32:780–796PubMedCrossRefGoogle Scholar
  16. Chang CA (1991) Lanthanide magnetic resonance imaging contrast agents: thermodynamic, kinetic, and structural properties of lanthanide (III) macrocyclic complexes. Eur J Solid State Inorg Chem 28:237–244Google Scholar
  17. Chang CA (1993) Magnetic resonance imaging contrast agents design and physicochemical properties of gadodiamide. Invest Radiol 28(suppl 1):S21–S27PubMedGoogle Scholar
  18. Chang CA, Sieving PF, Watson AD, Dewey TM, Karpishin TB, Raymond KN (1992) Ionic versus nonionic MR imaging contrast media: operational definitions. J Magn Reson Imaging 2:95–98PubMedCrossRefGoogle Scholar
  19. Cohan RH, Leder RA, Herzberg AJ, Hedlund LW, Wheeler CT, Beam CA, Nadel SN, Dunnick NR (1991) Extravascular toxicity of two magnetic resonance contrast agents. Preliminary experience in the rat. Invest Radiol 26:224–226PubMedCrossRefGoogle Scholar
  20. Corot C, Idée JM, Hentsch AM, Santus R, Mallet C, Goulas V, Bonnemain B, Meyer D (1998) Structure-activity relationship of macrocyclic and linear gadolinium chelates: investigation of transmetallation effect on the zinc-dependent metallopeptidase angiotensin-converting enzyme. J Magn Reson Imaging 8:695–702PubMedCrossRefGoogle Scholar
  21. Corot C, Violas X, Robert P, Gagneur G, Port M (2003) Comparison of different types of blood pool agents (P792, MS325, USPIO) in a rabbit MR angiography-like protocol. Invest Radiol 38:311–319PubMedCrossRefGoogle Scholar
  22. Cowper SE, Boyer PJ (2006) Nephrogenic systemic fibrosis: an update. Curr Rheumatol Rep 8:151–157PubMedCrossRefGoogle Scholar
  23. Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE (2000) Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 356:1000–1001PubMedCrossRefGoogle Scholar
  24. De Haen C, Cabrini M, Akhnana L, Ratti D, Calabi L, Gozzini L (1999) Gadobenate dimeglumine 0.5 M solution for injection (MultiHance) pharmaceutical formulation and physicochemical properties of a new magnetic resonance imaging contrast medium. J Comput Assist Tomogr 23(Suppl 1):S161–S168PubMedGoogle Scholar
  25. Desreux JF (1980) Nuclear magnetic resonance spectroscopy of lanthanide complexes with a tetraacetic tetraaza macrocycle. Unusual conformation properties. Inorg Chem 19:1319–1324CrossRefGoogle Scholar
  26. Desreux JF, Barthelemy PP (1988) Highly stable lanthanide macrocyclic complexes: in search of new contrast agents for NMR imaging. Nucl Med Biol 1:9–15Google Scholar
  27. Dharnidharka VR, Wesson SK, Fennell RS (2006) Gadolinium and nephrogenic fibrosing dermopathy in pediatric patients. Pediatr Nephrol 22:1395PubMedCrossRefGoogle Scholar
  28. Evans CH (1990) Biochemistry of the lanthanides. Plenum Press, LondonGoogle Scholar
  29. Evenepoel P, Zeegers M, Segaert S, Claes K, Kuypers D, Maes B, Flamen P, Fransis S, Vanrenterghem Y (2004) Nephrogenic fibrosing dermopathy: a novel, disabling disorder in patients with renal failure. Nephrol Dial Transplant 19:469–473PubMedCrossRefGoogle Scholar
  30. Fossheim R, Dugstat H, Dahl G (1991) Structure-stability relashionships of Gd(III) ion complexes for magnetic resonance imaging. J Med Chem 34:819–826PubMedCrossRefGoogle Scholar
  31. Galan A, Cowper SE, Bucala R (2006) Nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy). Curr Opin Rheumatol 18:614–617PubMedCrossRefGoogle Scholar
  32. Gibby WA, Gibby KA, Gibby WA (2004) Comparison of Gd-DTPA-BMA (Omniscan) versus Gd-HP-DO3A (ProHance) retention in human bone tissue by inductively coupled plasma atomic emission spectroscopy. Invest Radiol 39:138–142PubMedCrossRefGoogle Scholar
  33. Gries H, Miklautz H (1984) Some physicochemical properties of gadolinium-DTPA complex, a contrast agent for IRM. Physiol Chem Phys Med NMR 16:105–112PubMedGoogle Scholar
  34. Grobner T (2006) Gadolinium: a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 21:1104–1108PubMedCrossRefGoogle Scholar
  35. Harrison A, Walker CA, Pereira KA, Parker D, Royle L, Pulukkody K, Norman TJ (1993) Hepato-biliary and renal excretion in mice of charged and neutral gadolinium complexes of cyclic tetra-aza-phosphinic and carboxylic acids. Magn Reson Imaging 11:761–770PubMedCrossRefGoogle Scholar
  36. Ibrahim MA, Haughton VM, Hyde JS (1994) Enhancement of intervertebral disks with gadolinium complexes: comparison of an ionic and a nonionic medium in an animal model. AJNR Am J Neuroradiol 15:1907–1910PubMedGoogle Scholar
  37. Idée JM, Port M, Raynal I, Schaefer M, Le Greneur S, Corot C (2006) Clinical and biological consequences of transmetallation induced by contrast agents for magnetic resonance imaging: a review. Fundam Clin Pharmacol 20:563–576PubMedCrossRefGoogle Scholar
  38. Inigo P, Campistol JM, Lario S, Piera C, Campos B, Bescos M, Oppenheimer F, Rivera F (2001) Effects of losartan and amlodipine on intrarenal hemodynamics and TGF-beta(1) plasma levels in a crossover trial in renal transplant recipients. J Am Soc Nephrol 12:822–827PubMedGoogle Scholar
  39. Itoh N, Kawakita M (1984) Characterization of Gd3+ and Tb3+ binding sites on Ca2+, Mg2+-adenosine triphosphatase of sarcoplasmic reticulum. Tokyo J Biochem 95:661–669Google Scholar
  40. Jackson GE, Wynchank S, Woudenberg M (1990) Gadolinium(III) complex equilibria: the implications for Gd(III) MRI contrast agents. Magn Reson Med 16:57–66PubMedCrossRefGoogle Scholar
  41. Joffe P, Thomsen HS, Meusel M (1998) Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. Acad Radiol 5:491–502PubMedCrossRefGoogle Scholar
  42. Kanal E, Barkovich AJ, Bell C, Borgstede JP, Bradley WG Jr, Froelich JW, Gilk T, Gimbel JR, Gosbee J, Kuhni-Kaminski E, Lester JW Jr, Nyenhuis J, Parag Y, Schaefer DJ, Sebek-Scoumis EA, Weinreb J, Zaremba LA, Wilcox P, Lucey L, Sass N (2007) ACR guidance document for safe MR practices. Am J Roentgenol 188:1–27CrossRefGoogle Scholar
  43. Khanna A, Kapur S, Sharma VK, Li B, Suthanthiran M (1997) In vivo hyperexpression of transforming growth-factor-beta 1 in mice: stimulation by cyclosporine. Transplantation 63:1037–1039PubMedCrossRefGoogle Scholar
  44. Kimura J, Ishiguchi T, Matsuda J, Ohno R, Nakamura A, Kamei S, Ohno K, Kawamura T, Murata K (2005) Human comparative study of zinc and copper excretion via urine after administration of magnetic resonance imaging contrast agents. Rad Med 23:322–326Google Scholar
  45. Kumar K (1997) Macrocyclic polyamino carboxylate complexes of Gd(III) as magnetic resonance imaging contrast agents. J Alloys Comp 249:163–172CrossRefGoogle Scholar
  46. Kumar K, Tweedle MF (1993) Macrocyclic polyaminocarboxylate complexes of lanthanides as magnetic resonance imaging contrast agents. Pure Appl Chem 65:515–520CrossRefGoogle Scholar
  47. Kumar K, Chang CA, Tweedle MF (1993) Equilibrium and kinetic studies of lanthanide complexes of macrocyclic polyamino carboxylates. Inorg Chem 32:587–593CrossRefGoogle Scholar
  48. Kumar K, Jin T, Wang X, Desreux JF, Tweedle MF (1994) Effect of ligand basicity on the formation and dissociation equilibria and kinetics of Gd3+ complexes of macrocyclic polyamino carboxylates. Inorg Chem 33:3823–3829CrossRefGoogle Scholar
  49. Kumar K, Tweedle MF, Malley MF, Gougoutas JZ (1995) Synthesis, stability, and crystal structure studies of some Ca2+, Cu2+, and Zn2+ complexes of macrocyclic polyamino carboxylates. Inorg Chem 34:6472–6480CrossRefGoogle Scholar
  50. Laurent S, Vander Elst L, Copoix F, Muller RN (2001) Stability of MRI paramagnetic contrast media. A proton relaxometric protocol for transmetallation assessment. Invest Radiol 36:115–122PubMedCrossRefGoogle Scholar
  51. Laurent S, Vander Elst L, Muller RN (2006) Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents. Contrast Media Mol Imaging 1:128–137PubMedCrossRefGoogle Scholar
  52. Lorusso V, Arbughi T, Tirone P, de Haen C (1999) Pharmacokinetics and tissue distribution in animals of gadobenate ion, the magnetic resonance imaging contrast enhancing component of gadobenate dimeglumine 0.5 M solution for injection (MultiHance). J Comput Assist Tomogr 23(Suppl 1):S181–S194PubMedGoogle Scholar
  53. Mackay-Wiggan JM, Cohen DJ, Hardy MA et al. (2003) Nephrogenic fibrosing dermopathy (scleromyxoedema-like illness of renal disease). J Am Acad Dermatol 48:55–60PubMedCrossRefGoogle Scholar
  54. Magerstät M, Gansow OT, Brechiel MW, Colcher D, Baltzer L, Knop RH, Girton ME, Naegle M (1986) GdDOTA: an alternative to GdDTPA as T1,2 relaxation agent for NMR imaging or spectroscopy. Magn Reson Imaging 3:808–812Google Scholar
  55. Mann JS (1993) Stability of gadolinium complexes in vitro and in vivo. J Comput Assist Tomogr 17(suppl 1):S19–S23PubMedGoogle Scholar
  56. Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, Thomsen HS (2006) Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 17:2359–2362PubMedCrossRefGoogle Scholar
  57. McMurry TJ, Pippin CG, Wu C, Deal KA, Brechbiel MW, Mirzadeh S, Gansow OA (1998) Physical parameters and biological stability of yttrium(III) diethylenetriaminepentaacetic acid derivative conjugates. J Med Chem 27;41:3546–3549CrossRefGoogle Scholar
  58. Mendoza FA, Artlett CM, Sandorfi N, Latinis K, Piera-Velazquez S, Jimenez SA (2006) Description of 12 cases of nephrogenic fibrosing dermopathy and review of the literature. Semin Arthritis Rheum 35:238–249PubMedCrossRefGoogle Scholar
  59. Meyer D, Schaefer M, Bonnemain B (1988) Gd-DOTA, a potential MRI contrast agent. Current status of physicochemical knowledge. Invest Radiol 23:S232–S235PubMedCrossRefGoogle Scholar
  60. Morcos SK (2007a) Nephrogenic systemic fibrosis following the administration of extracellular gadolinium-based contrast agents: is the stability of the contrast agent molecule an important factor in the pathogenesis of this condition ? Br J Radiol 80:73–76PubMedCrossRefGoogle Scholar
  61. Morcos SK (2007b) Reply to Schmitt-Willich and Tweedle MF. Br J Radiol 80:584–585CrossRefGoogle Scholar
  62. Moreau J, Guillon E, Pierrard JC, Rimbault J, Port M, Aplincourt M (2004) Complexing mechanism of the lanthanide cations Eu3+, Gd3+, and Tb3+ with1,4,7,10–tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (dota)-characterization of three successive complexing phases: study of the thermodynamic and structural properties of the complexes by potentiometry, luminescence spectroscopy, and EXAFS. Eur J Chem 10:5218–5232CrossRefGoogle Scholar
  63. Muller RN, Radüchel B, Laurent S, Platzek J, Piérart C, Mareski P, Vander Elst L (1999) Physicochemical characterization of MS-325, a new gadolinium complex, by multinuclear relaxometry. Eur J Inorg Chem 11:1949–1955CrossRefGoogle Scholar
  64. Okazaki O, Kurata T, Yoshioka N, Hakusui H (1996) Pharmacokinetics and stability of caldiamide sodium in rats. Arzneimittelforschung 46:79–83PubMedGoogle Scholar
  65. Perazella MA (2007) Nephrogenic systemic fibrosis, kidney disease and gadolinium: is there a link? Clin J Am Soc Nephrol 2:200–202PubMedCrossRefGoogle Scholar
  66. Pollet R, Marx D (2007) Ab initio simulation of a gadolinium-based magnetic resonance imaging contrast agent in aqueous solution. J Chem Phys 14:126:181102CrossRefGoogle Scholar
  67. Port M, Corot C, Violas X, Robert P, Raynal I, Gagneur G (2005) How to compare the efficiency of albumin-bound and nonalbumin-bound contrast agents in vivo: the concept of dynamic relaxivity. Invest Radiol 40(9):565–573PubMedCrossRefGoogle Scholar
  68. Port M, Idée JM, Medina C, Dencausse A, Corot C (2008) Stability of gadolinium chelates and their biological consequences: new data and some comments. Br J Radiol 81:258–259PubMedCrossRefGoogle Scholar
  69. Pulukkody KP, Norman TJ, Parker D, Royle L, Broan CJ (1993) Synthesis of charged and uncharged complexes of gadolinium and yttrium with cyclic polyazaphosphinic acid ligands for in vivo applications. J Chem Soc Perkin Trans 2:605–620Google Scholar
  70. Puttagunta NR, Gibby WA, Puttagunta VL (1996a) Comparative transmetallation kinetics and thermodynamic stability of gadolinium-DTPA bis-glucosamide and other magnetic resonance imaging contrast media. Invest Radiol 10:619–624CrossRefGoogle Scholar
  71. Puttagunta NR, Gibby WA, Smith GT (1996b) Human in vivo comparative study of zinc and copper transmetallation after administration of magnetic resonance imaging contrast agents. Invest Radiol 31:739–742PubMedCrossRefGoogle Scholar
  72. Rohrer M, Bauer H, Mintorovitch J, Requardt M, Weinmann HJ (2005) Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Invest Radiol 40:715–724PubMedCrossRefGoogle Scholar
  73. Rothermel GL, Rizkalla EN, Choppin GR (1997) The kinetic of exchange between a lanthanide ion and the gadolinium complex of N,N″-bis(2-methoxyethylamide-carbamoylmethyl)-diethylenetriamine-N,N′,N″-triacetate. Inorganic Chim Acta 262:133–138CrossRefGoogle Scholar
  74. Sarka L, Burai L, Brücher E (2000) The rates of the exchange reactions between [Gd(DTPA)]2− and the endogenous ions Cu2+ and Zn2+: a kinetic model for the prediction of the in vivo stability of [Gd(DTPA)]2−, used as a contrast agent in magnetic resonance imaging. Chem Eur J 6(4):719–724CrossRefGoogle Scholar
  75. Sarka L, Burai L, Kiraly R, Zekany L, Brücher E (2002) Studies on the kinetic stabilities of the Gd(3+) complexes formed with theN-mono(methylamide), N′-mono(methylamide) and N,N″-bis(methylamide) derivativesof diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid. J Inorg Biochem 25;91:320–326CrossRefGoogle Scholar
  76. Schmitt-Willich H (2007) Stability of linear and macrocyclic gadolinium based contrast agents. Br J Radiol 80:581–582PubMedCrossRefGoogle Scholar
  77. Schmitt-Willich H, Brehm M, Ewers CL, Michl G, Müller-Fahrnow A, Petrov O, Platzek J, Radüchel B, Sülzle D (1999) Synthesis and physicochemical characterization of a new gadolinium chelate: the liver-specific magnetic resonance imaging contrast agent Gd-EOB-DTPA. Inorg Chem 22;38:1134–1144CrossRefGoogle Scholar
  78. Spinazzi A, Lorusso V, Pirovano G, Kirchin M (1999) Safety, tolerance, biodistribution, and MR imaging enhancement of the liver with gadobenate dimeglumine: results of clinical pharmacologic and pilot imaging studies in nonpatient and patient volunteers. Acad Radiol 6:282–291PubMedCrossRefGoogle Scholar
  79. Steger-Hartmann T, Graham PB, Müller S, Schweinfurth H (2006) Preclinical safety assessment of Vasovist (Gadofosveset trisodium), a new magnetic resonance imaging contrast agent for angiography. Invest Radiol 41:449–459PubMedCrossRefGoogle Scholar
  80. Swaminathan S, Ahmed I, McCarthy JT, Albright RC, Pittelkow MR, Caplice NM, Griffin MD, Leung N (2006) Nephrogenic fibrosing dermopathy and high-dose erythropoietin therapy. Ann Intern Med 145:234–235PubMedGoogle Scholar
  81. Thakral C, Alhariri J, Abraham JL (2007) Long-term retention of gadolinium in tissues from nephrogenic systemic fibrosis patient after multiple gadolinium-enhanced MRI scans: case report and implications. Contrast Media Mol Imaging 2(4):199–205PubMedCrossRefGoogle Scholar
  82. Ting WW, Seabury Stone M, Madison KC, Kurtz K (2003) Nephrogenic fibrosing dermopathy with systemic involvement. Arch Dermatol 139:903–906PubMedCrossRefGoogle Scholar
  83. Toth E, Brücher E, Lazar I, Toth I (1994) Kinetics of formation and dissociation of lanthanide(III)-DOTA complexes. Inorg Chem 33:4070–4076CrossRefGoogle Scholar
  84. Toth E, Kiraly R, Platzek J, Radüchel B, Brücher E (1996) Equilibrium and kinetic studies on complexes of 10-[2,3-dihydroxy-(1-hydroxymethyl)-propyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetate. Inorganica Acta 249:191–199CrossRefGoogle Scholar
  85. Tweedle MF (1992) Physicochemical properties of gadoteridol and other magnetic resonance contrast agents. Invest Radiol 27(Suppl 1):S2–S6PubMedGoogle Scholar
  86. Tweedle MF (2007) “Stability” of gadolinium chelates. Br J Radiol 80:583–584PubMedCrossRefGoogle Scholar
  87. Tweedle MF, Eaton SM, Eckelman WC, Gaughan GT, Hagan JJ, Wedeking P, Yost FJ (1988) Comparative chemical structure and pharmacokinetics of MRI contrast agents. Invest Radiol 23:S236–S239PubMedCrossRefGoogle Scholar
  88. Tweedle MF, Hagan JJ, Kumar K, Mantha S, Chang CA (1991) Reaction of gadolinium chelates with endogenously available ions. Magn Reson Imaging 9:409–415PubMedCrossRefGoogle Scholar
  89. Tweedle MF, Wedeking P, Kumar K (1995) Biodistribution of radiolabeled, formulated gadopentetate, gadoteridol, gadoterate, and gadodiamide in mice and rats. Invest Radiol 30:372–380PubMedCrossRefGoogle Scholar
  90. Uggeri F, Aime S, Anelli PL, Botta M, Brocchetta M, de Haën C, Ermondi G, Grandi M, Paoli P (1995) Novel contrast agents for magnetic resonance imaging. Synthesis and characterization of the ligand BOPTA and its Ln(III) complexes (Ln = Gd, La, Lu). X-ray structure of disodium (TPS-9–145337286-C-S)-[4-Carboxy-5,8,11-tris(carboxymethyl)-1-phenyl-2-oxa-5,8,11-triazatridecan-13-oato(5-)]gadolinate(2-) in a mixture with its enantiomer. Inorg Chem 34:633–642CrossRefGoogle Scholar
  91. Vander Elst L, Van Haverbeke Y, Goudemant JF, Muller RN (1994) Stability assessment of gadolinium complexes by P-31 and H-1 relaxometry. Magn Reson Med 31:437–444PubMedCrossRefGoogle Scholar
  92. Vander Elst L, Maton F, Laurent S, Seghi F, Chapelle F, Muller RN (1997) A multinuclear MR study of Gd-EOB-DTPA: comprehensive preclinical characterization of an organ specific MRI contrast agent. Magn Reson Med 38(4):604–614PubMedCrossRefGoogle Scholar
  93. Vander Elst L, Chapelle F, Laurent S, Muller RN (2001) Stereospecific binding of MRI contrast agents to human serum albumin: the case of Gd-(S)-EOB-DTPA (Eovist) and its (R) isomer. J Biol Inorg Chem 6:196–200PubMedCrossRefGoogle Scholar
  94. Varadarajan JA, Crofts SP, Carvalho JF, Fellmann JD, Kim SH, Chang CA, Watson AD (1994) The synthesis and evaluation of macrocyclic gadolinium-DTPA-bis(amide) complexes as magnetic resonance imaging contrast agents. Invest Radiol 29(Suppl 2):S18–S20PubMedCrossRefGoogle Scholar
  95. Wang X, Jin T, Comblin V, Lopez-Mut A, Merciny E, Desreux JF (1992) A kinetic investigation of the lanthanide DOTA chelates. Stability and rates of formation and of dissociation of a macrocyclic gadolinium (III) polyaza polycarboxylic MRI contrast agent. Inorg Chem 31:1095–1099CrossRefGoogle Scholar
  96. Wedeking P, Kumar K, Tweedle MF (1992) Dissociation of gadolinium chelates in mice: relationship to chemical characteristics. Magn Reson Imaging 10:641–648PubMedCrossRefGoogle Scholar
  97. Wedeking P, Tweedle M (1988) Comparison of the biodistribution of 153Gd-labeled, Gd(DTPA)2-, Gd(DOTA)- and Gd(acetate)n in mice. Nucl Med Biol 15:395–402Google Scholar
  98. White DH, de Learie LA, Moore DA, Wallace RA, Dunn TJ, Cacheris WP, Imura H, Choppin GR (1991) The thermodynamics of complexation of lanthanide (III) DTPA-bisamide complexes and their implication for stability and solution structure. Invest Radiol 26(suppl 1):S226–S228PubMedGoogle Scholar
  99. White GW, Gibby WA, Tweedle MF (2006) Comparison of Gd(DTPA-BMA) (Omniscan) versus Gd(HP-DO3A) (ProHance) relative to gadolinium retention in human bone tissue by inductively coupled mass spectroscopy. Invest Radiol 41:272–278PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Marc Port
    • 1
    Email author
  • Jean-Marc Idée
    • 1
  • Christelle Medina
    • 1
  • Caroline Robic
    • 1
  • Monique Sabatou
    • 1
  • Claire Corot
    • 1
  1. 1.Guerbet, Research DivisionAulnay-sous-BoisFrance

Personalised recommendations