Contrast Media pp 175-180 | Cite as

Gadolinium Chelates and Stability

  • Sameh K. Morcos
Part of the Medical Radiology book series (MEDRAD)


The gadolinium ions which enhance the signals in MR images are very toxic, so in the contrast medium molecule they have to be strongly attached to a chelate to avoid adverse effects. The linear chelate molecules are open chains which can fold and unfold off the gadolinium ion with ease. In contrast, the macrocyclic chelate molecules are rigid rings of almost optimal size to cage the gadolinium ion. Experimental data, both in vitro and in vivo, and clinical observations, have confirmed the lower stability of the linear gadolinium-based molecules compared to the more stable macrocyclic agents.


Nephrogenic Systemic Fibrosis Zinc Excretion Hydroxypropyl Group Subtotal Nephrectomy Macrocyclic Chelate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 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, Chichester, pp 249–257 (Chap. 6)Google Scholar
  2. Cacheris WP, Quay SC, Rocklage SM (1990) The relationship between thermodynamics and the toxicity of gadolinium complexes. Magn Reson Imag 8:467–481CrossRefGoogle Scholar
  3. Corot C, Idee JM, Hentsch AM et al (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 Imag 8:695–702CrossRefGoogle Scholar
  4. Dawson P (1999) Gadolinium chelates: chemistry. In: Dawson P, Cosgrove DO, Grainger RG (eds) Textbook of contrast media. Isis Medical Media, Oxford, pp 291-296 (Chapt. 22)Google Scholar
  5. Desreux JF, Gilsoul D (1999) Chemical synthesis of paramagnetic complexes. In: Thomsen HS, Muller RN, Mattrey (eds) Trends in contrast media. Springer, Heidelberg, pp 161–169 (Chap. 15)Google Scholar
  6. Douthwaite JA, Johnson TS, Haylor JL et al (1999) Effects of transforming growth factor-beta1 on renal extracellular matrix components and their regulating proteins. J Am Soc Nephrol 10:2109–2119PubMedGoogle Scholar
  7. Frenzel T, Lengsfeld P, Schirmer H et al (2008) Stability of gadolinium based magnetic resonance imaging contrast agents in human serum at 37 °C. Invest Radiol 43:817–828PubMedCrossRefGoogle Scholar
  8. Fretellier N, Idée JM, Dencausse A et al (2011) Comparative in vivo dissociation of gadolinium chelates in renally impaired rats: a relaxometry study. Invest Radiol 46:292–300PubMedCrossRefGoogle Scholar
  9. Gibby WA, Gibby KA, Gibby WA (2004) Comparison of Gd DTPA-BMA (Omniscan) versus Gd-Hp-DO3A (ProHance) retention in human bone tissue by inductive coupled plasma atomic emission spectroscopy. Invest Radiol 39:138–142PubMedCrossRefGoogle Scholar
  10. Green RWF, Krestin GP (2006) Non-tissue specific extra cellular MR contrast media. In: Thomsen (ed) Contrast media. Safety issues and ESUR guidelines. Springer, Heidelberg, pp 107–112 (Chap. 16)Google Scholar
  11. Haylor J, Dencausse A, Vickers M et al (2012) Skin gadolinium following MRI contrast agents in a rat model of nephrogenic systemic fibrosis. Radiology 263:107–116PubMedCrossRefGoogle Scholar
  12. Idee J-M, Port M, Raynal I et al (2006) Clinical and biological consequences of transmetallation induced by contrast agents for magnetic resonance imaging: a review. Fundam Clin Pharmacol 20:563–576PubMedCrossRefGoogle Scholar
  13. Kimura J, Ishguchi T, Matsuda J et al (2005) Human comparative study of zinc and copper excretion via urine after administration of magnetic resonance imaging contrast agents. Radiation Med 23:322–326Google Scholar
  14. Kumar K (1997) Macrocyclic polyamino carboxylate complexes of Gd(III) as magnetic resonance imaging contrast agents. J Alloys Compounds 249:163–172CrossRefGoogle Scholar
  15. Laurent S, Elst LV, Copoix F, Muller RN (2001) Stability of MRI paramagnetic contrast media, a proton relaxometric protocol for transmetallation assessment. Invest Radiol 36:115–122PubMedCrossRefGoogle Scholar
  16. Laurent S, Elst LV, Copoix F, 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
  17. Morcos SK (2007) 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
  18. Morcos SK (2011) Experimental studies investigating the pathophysiology of nephrogenic systemic fibrosis; what did we learn so far? Eur Radiol 21:496–500PubMedCrossRefGoogle Scholar
  19. Morcos SK, Thomsen HS, Webb JAW (2002) Members of the contrast media safety committee of the european society of urogenital radiology (ESUR) Dialysis and contrast media. Eur Radiol 12:3026–3030Google Scholar
  20. Perazella MA (2007) Nephrogenic systemic fibrosis, kidney disease and gadolinium: is there a link? Clin J Am Soc Nephrol 2:200–2002PubMedCrossRefGoogle Scholar
  21. Pietsch H, Lengsfeld P, Jost G et al (2009) Long-term retention of gadolinium in the skin of rodents following the administration of gadolinium-based contrast agents. Eur Radiol 19:1417–1424PubMedCrossRefGoogle Scholar
  22. Port M, Idée JM, Medina C et al (2008) Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates and their possible clinical consequences: a critical review. Biometals 21:469–490PubMedCrossRefGoogle Scholar
  23. Puttagunta NR, Gibby WA, Smith GT (1996) Human in vivo comparative study of zinc and copper transmetallation after administration of magnetic resonance imaging contrast agents. Invest Radiol 12:739–742CrossRefGoogle Scholar
  24. Rofsky NM, Sherry AD, Lenkinski RE (2008) Nephrogenic systemic fibrosis: a chemical perspective. Radiology 247:608–612PubMedCrossRefGoogle Scholar
  25. Sieber MA, Lengsfeld P, Frenzel T et al (2008) Preclinical investigation to compare different gadolinium-based agents regarding their propensity to release gadolinium in vivo and to trigger nephrogenic systemic fibrosis-like lesions. Eur Radiol 18:2164–2173PubMedCrossRefGoogle Scholar
  26. Thomsen HS, Morcos SK, Dawson P (2006) Is there a causal relation between the administration gadolinium based contrast media and the development of nephrogenic systemic fibrosis (NSF)? Clin Radiol 61:905–906PubMedCrossRefGoogle Scholar
  27. Tweedle MF (1992) Physicochemical properties of gadoteridol and other magnetic resonance contrast agents. Invest Radiol 27:S2–S6PubMedCrossRefGoogle Scholar
  28. Tweedle MF (2007) Stability of gadolinium chelates (letter to the Editor). Br J Radiol 80:583–584PubMedCrossRefGoogle Scholar
  29. Tweedle MF, Gaughan GT, Hagan J et al (1988) Considerations involving paramagnetic coordination compounds as useful NMR contrast agents. Nucl Med Biol, Int J Radiat Appl Instrum. Part B 15:31–36Google Scholar
  30. 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
  31. Wedeking P, Kumar K, Tweedle MF (1992) Dissociation of gadolinium chelates in mice: relationship to chemical characteristics. Magn Reson Imaging 10:641–648PubMedCrossRefGoogle Scholar
  32. 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 plasma mass spectroscopy. Invest Radiol 41:272–278PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Diagnostic ImagingUniversity of SheffieldSheffieldUK

Personalised recommendations