Skip to main content
Top
Published in: La radiologia medica 6/2016

01-06-2016 | CONTRAST MEDIA

Gadolinium-based contrast agents: did we miss something in the last 25 years?

Authors: Bruno Beomonte Zobel, Carlo Cosimo Quattrocchi, Yuri Errante, Rosario Francesco Grasso

Published in: La radiologia medica | Issue 6/2016

Login to get access

Abstract

In the last 24 months, several clinical and experimental studies, suggested first and demonstrated later, a progressive concentration of Gadolinium in the brain of normal renal function patients, following repeated injections of some of the commercially approved Gadolinium-Based Contrast Agents. Although, till now, Gadolinium brain deposits have not been associated to any kind of neurological signs or symptoms, they oblige the radiology community to modify the actual approach in using Gadolinium contrast media in daily practice, to reduce unknown possible risks for patients.
Literature
1.
go back to reference Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Gadolinium (III) chelates as MRI contrast agents: structure, dynamics and applications. Chem Rev 99:2293–2352CrossRefPubMed Caravan P, Ellison JJ, McMurry TJ, Lauffer RB (1999) Gadolinium (III) chelates as MRI contrast agents: structure, dynamics and applications. Chem Rev 99:2293–2352CrossRefPubMed
2.
go back to reference Palasz A, Czekaj P (2000) Toxicological and cytophysiological aspects of lanthanides action. Acta Biochim Pol 47:1107–1114PubMed Palasz A, Czekaj P (2000) Toxicological and cytophysiological aspects of lanthanides action. Acta Biochim Pol 47:1107–1114PubMed
3.
go back to reference Lowe A, Balzer T, Hirt U (2005) Interference of Gadolinium containing contrast-enhancing agents with colorimetric calcium laboratory testing. Invest Radiol 40:521–525CrossRefPubMed Lowe A, Balzer T, Hirt U (2005) Interference of Gadolinium containing contrast-enhancing agents with colorimetric calcium laboratory testing. Invest Radiol 40:521–525CrossRefPubMed
4.
go back to reference Swaminathan S, Horn TD, Pellowski D et al (2007) Nephrogenic systemic fibrosis, Gadolinium and iron mobilization. New Engl J Med 357:720–722CrossRefPubMed Swaminathan S, Horn TD, Pellowski D et al (2007) Nephrogenic systemic fibrosis, Gadolinium and iron mobilization. New Engl J Med 357:720–722CrossRefPubMed
5.
go back to reference Ersoy H, Rybicki FJ (2007) Biochemical safety profiles of Gadolinium-based extracellular contrast agents and nephrogenic systemic fibrosis. J Magn Reson Imaging 25:1190–1197CrossRef Ersoy H, Rybicki FJ (2007) Biochemical safety profiles of Gadolinium-based extracellular contrast agents and nephrogenic systemic fibrosis. J Magn Reson Imaging 25:1190–1197CrossRef
6.
go back to reference Yang L, Krefting I, Gorovets A et al (2012) Nephrogenic systemic fibrosis and class labeling of Gadolinium-based contrast agents by the food and drug administration. Radiology 265:248–253CrossRefPubMed Yang L, Krefting I, Gorovets A et al (2012) Nephrogenic systemic fibrosis and class labeling of Gadolinium-based contrast agents by the food and drug administration. Radiology 265:248–253CrossRefPubMed
7.
go back to reference Idee JM, 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 20:563–576CrossRefPubMed Idee JM, 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 20:563–576CrossRefPubMed
8.
go back to reference Runge VM (2015) Commentary on T1-weighted hypersignal in the deep cerebellar nuclei after repeated administrations of Gadolinium-based contrast agents in healthy rats. Invest Radiol 50:481–482CrossRefPubMed Runge VM (2015) Commentary on T1-weighted hypersignal in the deep cerebellar nuclei after repeated administrations of Gadolinium-based contrast agents in healthy rats. Invest Radiol 50:481–482CrossRefPubMed
9.
go back to reference Prince MR, Zhang H, Zou Z, Staron RB, Brill PW (2011) Incidence of immediate Gadolinium contrast media reactions. AJR 196:W138–W143CrossRefPubMed Prince MR, Zhang H, Zou Z, Staron RB, Brill PW (2011) Incidence of immediate Gadolinium contrast media reactions. AJR 196:W138–W143CrossRefPubMed
10.
go back to reference Bruder O, Schneider S, Pilz G et al (2015) Update on acute adverse reaction to Gadolinium based contrast agents in cardiovascular MR. Large multi-national and multi-ethnical population experience with 37.788 patients from the EuroCMR registry. J Cardiovasc Magn Reson 17:14 (Epub ahead of print) CrossRef Bruder O, Schneider S, Pilz G et al (2015) Update on acute adverse reaction to Gadolinium based contrast agents in cardiovascular MR. Large multi-national and multi-ethnical population experience with 37.788 patients from the EuroCMR registry. J Cardiovasc Magn Reson 17:14 (Epub ahead of print) CrossRef
11.
go back to reference Grobner T (2006) Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis ? Nephrol Dial Transpl 21:1104–1108CrossRef Grobner T (2006) Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis ? Nephrol Dial Transpl 21:1104–1108CrossRef
12.
go back to reference Marckmann P, Skov L, Rossen K et al (2006) Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 17:2359–2362CrossRefPubMed Marckmann P, Skov L, Rossen K et al (2006) Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 17:2359–2362CrossRefPubMed
13.
go back to reference Idee JM, Port M, Dencausse A, Lancelot E, Corot C (2009) Involvement of Gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: an update. Radiol Clin North Am 47:855–869CrossRefPubMed Idee JM, Port M, Dencausse A, Lancelot E, Corot C (2009) Involvement of Gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: an update. Radiol Clin North Am 47:855–869CrossRefPubMed
14.
go back to reference Idee JM, Fretellier N, Robic C, Corot C (2014) The role of Gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: a critical update. Crit Rev Toxicol 44:895–913CrossRefPubMed Idee JM, Fretellier N, Robic C, Corot C (2014) The role of Gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: a critical update. Crit Rev Toxicol 44:895–913CrossRefPubMed
15.
go back to reference Frenzel T, Lengsfeld P, Schirmer H, Hutter J, Weinmann HJ (2008) Stability of Gadolinium-based contrast agents in human serum at 37 °C. Invest Radiol 43:817–828CrossRefPubMed Frenzel T, Lengsfeld P, Schirmer H, Hutter J, Weinmann HJ (2008) Stability of Gadolinium-based contrast agents in human serum at 37 °C. Invest Radiol 43:817–828CrossRefPubMed
17.
go back to reference Larson KN, Gagnon AL, Darling MD, Patterson JW, Cropley TG (2015) Nephrogenic systemic fibrosis manifesting a decade after exposure to Gadolinium. JAMA Dermatol 151:1117–1120CrossRefPubMed Larson KN, Gagnon AL, Darling MD, Patterson JW, Cropley TG (2015) Nephrogenic systemic fibrosis manifesting a decade after exposure to Gadolinium. JAMA Dermatol 151:1117–1120CrossRefPubMed
18.
go back to reference Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D (2014) High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a Gadolinium-based contrast material. Radiology 270:834–841CrossRefPubMed Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D (2014) High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a Gadolinium-based contrast material. Radiology 270:834–841CrossRefPubMed
19.
go back to reference Errante Y, Cirimele V, Mallio CA, Di Lazzaro V, Beomonte Zobel B, Quattrocchi CC (2014) Progressive increase of T1 signal intensity of the dentate nucleus, on unenhanced Magnetic Resonance images, is associated with cumulative doses of intravenously administered Gadodiamide, in patients with normal renal function, suggesting dechelation. Invest Radiol 49:685–690CrossRefPubMed Errante Y, Cirimele V, Mallio CA, Di Lazzaro V, Beomonte Zobel B, Quattrocchi CC (2014) Progressive increase of T1 signal intensity of the dentate nucleus, on unenhanced Magnetic Resonance images, is associated with cumulative doses of intravenously administered Gadodiamide, in patients with normal renal function, suggesting dechelation. Invest Radiol 49:685–690CrossRefPubMed
20.
go back to reference Kanda T, Osawa M, Oba H et al (2015) High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic Gadolinium chelate administration. Radiology 275:803–809CrossRefPubMed Kanda T, Osawa M, Oba H et al (2015) High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic Gadolinium chelate administration. Radiology 275:803–809CrossRefPubMed
21.
go back to reference Quattrocchi CC, Mallio CA, Errante Y et al (2015) Gadodiamide and dentate nucleus T1 hyperintensity in patients with meningioma evaluated by multiple follow-up contrast-enhanced magnetic resonance examinations with no systemic interval therapy. Invest Radiol 50:470–472CrossRefPubMed Quattrocchi CC, Mallio CA, Errante Y et al (2015) Gadodiamide and dentate nucleus T1 hyperintensity in patients with meningioma evaluated by multiple follow-up contrast-enhanced magnetic resonance examinations with no systemic interval therapy. Invest Radiol 50:470–472CrossRefPubMed
22.
go back to reference Radbruch A, Weberling LD, Pascal J et al (2015) Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology 275:783–791CrossRefPubMed Radbruch A, Weberling LD, Pascal J et al (2015) Gadolinium retention in the dentate nucleus and globus pallidus is dependent on the class of contrast agent. Radiology 275:783–791CrossRefPubMed
23.
go back to reference Ramalho J, Castillo M, AlObaidy M et al. (2015) High signal intensity in globus pallidus and dentate nucleus on unenhanced T1-weighted MR images: evaluation of two linear Gadolinium-based contrast agents. Radiology 276:836–844CrossRef Ramalho J, Castillo M, AlObaidy M et al. (2015) High signal intensity in globus pallidus and dentate nucleus on unenhanced T1-weighted MR images: evaluation of two linear Gadolinium-based contrast agents. Radiology 276:836–844CrossRef
24.
go back to reference Gibby WA, Gibby KA, Gibby WA (2004) Comparison of Gd DTPA-BMA (Omniscan) versus GdHP-DO3A (ProHance) retention in human bone tissue by inductively coupled plasma atomic emission spectroscopy. Invest Radiol 39:138–142CrossRefPubMed Gibby WA, Gibby KA, Gibby WA (2004) Comparison of Gd DTPA-BMA (Omniscan) versus GdHP-DO3A (ProHance) retention in human bone tissue by inductively coupled plasma atomic emission spectroscopy. Invest Radiol 39:138–142CrossRefPubMed
25.
go back to reference 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 41:272–278CrossRefPubMed 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 41:272–278CrossRefPubMed
26.
go back to reference Darrah TH, Prutsman-Pfeiffer JJ, Poreda RJ, Ellen Campbell M, Hauschka PV, Hannigan RE (2009) Incorporation of excess Gadolinium into human bone from medical contrast agents. Metallomics 1:479–488CrossRefPubMed Darrah TH, Prutsman-Pfeiffer JJ, Poreda RJ, Ellen Campbell M, Hauschka PV, Hannigan RE (2009) Incorporation of excess Gadolinium into human bone from medical contrast agents. Metallomics 1:479–488CrossRefPubMed
27.
go back to reference McDonald RJ, McDonald JS, Kallmes DF et al (2015) Intracranial Gadolinium deposition after contrast-enhanced MR Imaging. Radiology 275:772–782CrossRefPubMed McDonald RJ, McDonald JS, Kallmes DF et al (2015) Intracranial Gadolinium deposition after contrast-enhanced MR Imaging. Radiology 275:772–782CrossRefPubMed
28.
go back to reference Kanda T, Fukusato T, Matsuda M et al (2015) Gadolinium-based contrast agents accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology 276:228–232CrossRefPubMed Kanda T, Fukusato T, Matsuda M et al (2015) Gadolinium-based contrast agents accumulates in the brain even in subjects without severe renal dysfunction: evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology 276:228–232CrossRefPubMed
29.
go back to reference Robert P, Lehericy S, Grand S et al (2015) T1-weighted hypersignal in the deep cerebellar nuclei following repeated administration of Gadolinium-based contrast agents in healthy rats: difference between linear and macrocyclic agents. Invest Radiol 50:473–480CrossRefPubMedPubMedCentral Robert P, Lehericy S, Grand S et al (2015) T1-weighted hypersignal in the deep cerebellar nuclei following repeated administration of Gadolinium-based contrast agents in healthy rats: difference between linear and macrocyclic agents. Invest Radiol 50:473–480CrossRefPubMedPubMedCentral
30.
go back to reference Kimura J, Ishiguchi T, Matsuda J et al (2005) Human comparative study of zinc and copper excretion via urine after administration of magnetic resonance imaging contrast agents. Radiat Med 23:322–326PubMed Kimura J, Ishiguchi T, Matsuda J et al (2005) Human comparative study of zinc and copper excretion via urine after administration of magnetic resonance imaging contrast agents. Radiat Med 23:322–326PubMed
31.
go back to reference Vorobiov M, Basok A, Tovbin D et al (2003) Iron-mobilizing properties of the Gadolinium-DTPA complex: clinical and experimental observations. Nephrol Dial Transpl 18:884–887CrossRef Vorobiov M, Basok A, Tovbin D et al (2003) Iron-mobilizing properties of the Gadolinium-DTPA complex: clinical and experimental observations. Nephrol Dial Transpl 18:884–887CrossRef
32.
go back to reference Idee JM, Berthommier C, Goulas V et al (1998) Haemodynamic effects of macrocyclic and linear Gadolinium chelates in rats: role of calcium and transmetallation. Biometals 11:113–123CrossRefPubMed Idee JM, Berthommier C, Goulas V et al (1998) Haemodynamic effects of macrocyclic and linear Gadolinium chelates in rats: role of calcium and transmetallation. Biometals 11:113–123CrossRefPubMed
33.
go back to reference Birka M, Wentker KS, Lusmoller E et al (2015) Diagnosis of Nephrogenic systemic fibrosis by means of elemental bioimaging and speciation analysis. Anal Chem 87:3321–3328CrossRefPubMed Birka M, Wentker KS, Lusmoller E et al (2015) Diagnosis of Nephrogenic systemic fibrosis by means of elemental bioimaging and speciation analysis. Anal Chem 87:3321–3328CrossRefPubMed
34.
go back to reference Fretellier N, Idee JM, Dencausse A et al (2011) Comparative in vivo dissociation of Gadolinium chelates in renally impaired rats: a relaxometry study. Invest Radiol 46:292–300CrossRefPubMed Fretellier N, Idee JM, Dencausse A et al (2011) Comparative in vivo dissociation of Gadolinium chelates in renally impaired rats: a relaxometry study. Invest Radiol 46:292–300CrossRefPubMed
35.
go back to reference Roberts DR, Holden K R (2015) Progressive increase of T1 signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images in the pediatric brain exposed to multiple doses of Gadolinium contrast. Brain Dev. doi:10.1016/j.braindev.2015.08.009 Roberts DR, Holden K R (2015) Progressive increase of T1 signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images in the pediatric brain exposed to multiple doses of Gadolinium contrast. Brain Dev. doi:10.​1016/​j.​braindev.​2015.​08.​009
36.
go back to reference Kanal E, Tweedle MF (2015) Residual or retained Gadolinium: practical implications for radiologists and our patients. Radiology 275:630–634CrossRefPubMed Kanal E, Tweedle MF (2015) Residual or retained Gadolinium: practical implications for radiologists and our patients. Radiology 275:630–634CrossRefPubMed
37.
go back to reference European Medicines Agency (EMA) Doc. Ref. EMEA/727399/2009 rev. EMEA/H/A-31/1097 London, 1 July 2010 European Medicines Agency (EMA) Doc. Ref. EMEA/727399/2009 rev. EMEA/H/A-31/1097 London, 1 July 2010
Metadata
Title
Gadolinium-based contrast agents: did we miss something in the last 25 years?
Authors
Bruno Beomonte Zobel
Carlo Cosimo Quattrocchi
Yuri Errante
Rosario Francesco Grasso
Publication date
01-06-2016
Publisher
Springer Milan
Published in
La radiologia medica / Issue 6/2016
Print ISSN: 0033-8362
Electronic ISSN: 1826-6983
DOI
https://doi.org/10.1007/s11547-015-0614-1

Other articles of this Issue 6/2016

La radiologia medica 6/2016 Go to the issue