Download PDF
CC BY-NC-ND 4.0 · Indian J Radiol Imaging 2017; 27(02): 141-147
DOI: 10.4103/0971-3026.209212
Genitourinary Radiology

Gadolinium based contrast agents in current practice: Risks of accumulation and toxicity in patients with normal renal function

Anju Ranga
Department of Radio-diagnosis, VMMC and Safdarjung Hospital, New Delhi, India
,
Yatish Agarwal
Department of Radio-diagnosis, VMMC and Safdarjung Hospital, New Delhi, India
,
Kanika Garg
Department of Radio-diagnosis, VMMC and Safdarjung Hospital, New Delhi, India
› Author Affiliations Financial support and sponsorship Nil.
› Further Information
Also available at
  PDF Download Permissions and Reprints

Abstract

Despite being decked as the most prized compounds in the nugget box of contrast agents for clinical radiologists, and carrying an indisputable tag of safety of the US Food and Drug Administration for close to three decades, all may not be seemingly well with the family of gadolinium compounds. If the first signs of violations of primum non nocere in relation to gadolinium-based contrast agents (GBCAs) appeared in the millennium year with the first published report of skin fibrosis in patients with compromised renal function, the causal relationship between the development of nephrogenic systemic fibrosis (NSF) and GBCAs, first proposed by two European groups in 2006, further precluded their use in renocompromised patients. The toxicity, pharmacokinetics, and pharmacodynamics of GBCAs, however, has come under hawk-eyed scrutiny with recent reports that gadolinium tends to deposit cumulatively in the brain of patients with normal hepatobiliary function and intact blood–brain barrier. While the jury on the long-term hazard significance of this critical scientific finding is still out, the use of GBCAs must be guided by due clinical diligence, avoidance of repeated doses, and preferring GBCAs with the best safety profiles.

Keywords

Gadolinium-based contrast agents - long-term toxicity - nephrogenic systemic fibrosis - neuronal deposition


Publication History

Article published online:
27 July 2021

© 2017. Indian Radiological Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Private Ltd.
A-12, Second Floor, Sector -2, NOIDA -201301, India

 

  • References

  • 1 Murphy KJ, Brunberg JA, Cohan RH. Adverse reactions to gadolinium contrast media: A review of 36 cases. AJR Am J Roentgenol 1996;167:847-9.
  • 2 Prince MR, Arnoldus C, Frisoli JK. Nephrotoxicity of high-dose gadolinium compared with iodinated contrast. J Magn Reson Imaging 1996;6:162-6.
  • 3 Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S, LeBoit PE. Scleromyxoedema-like cutaneous diseases in renal-dialysis patients. Lancet 2000; 356:1000-1.
  • 4 Grobner T. Gadolinium—A specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 2006;21:1104-8.
  • 5 Marckmann P, Skov L, Rossen K, Dupont A, Damholt MB, Heaf JG, et al. Nephrogenic systemic fibrosis: Suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 2006;17:2359-62.
  • 6 Available from: www.esur.org/fileadmin/content/NSF/NSF-ESUR_Guideline_Final.pdf [Last accessed on 2007 Jul 17].
  • 7 Hao D, Ai T, Goerner F, Hu X, Runge VM, Tweedle M. MRI contrast agents: Basic chemistry and safety. J Magn Reson Imaging 2012;36:1060-71.
  • 8 Runge VM. Safety of approved MR contrast media for intravenous injection. J Magn Reson Imaging 2000;12:205-13.
  • 9 Idée JM, Port M, Robic C, Medina C, Sabatou M, Corot C. Role of thermodynamic and kinetic parameters in gadolinium chelate stability. J Magn Reson Imaging 2009;30:1249-58.
  • 10 Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J Magn Reson Imaging 2009;30:1259-67.
  • 11 Frenzel T, Lengsfeld P, Schirmer H, Hütter J, Weinmann HJ. Stability of gadolinium based magnetic resonance imaging contrast agents in human serum at 37 degrees C. Invest Radiol 2008;43:817-28.
  • 12 Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D. High signal intensity in the dentate nucleus and globuspallidus on unenhanced T1-weighted MR images: Relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology 2014;270:834-41.
  • 13 Errante Y, Cirimele V, Mallio CA, Di Lazzaro V, Zobel BB, Quattrocchi CC. 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 2014; 49:685-90.
  • 14 Weberling LD, Kieslich PJ, Kickingereder P, Wick W, Bendszus M, Schlemmer HP, et al. Increased Signal Intensity in the Dentate Nucleus on Unenhanced T1-Weighted Images After GadobenateDimeglumine Administration. Invest Radiol 2015;50:743-8.
  • 15 Miller JH, Hu HH, Pokorney A, Cornejo P, Towbin R. MRI Brain Signal Intensity Changes of a Child During the Course of 35 Gadolinium Contrast Examinations. Pediatrics 2015;136:e1637-40
  • 16 Roberts DR, Holden KR. Progressive increase of T1 signal intensity in the dentate nucleus and globuspallidus on unenhanced T1-weighted MR images in the pediatric brain exposed to multiple doses of gadolinium contrast. Brain Dev 2016;38:331-6.
  • 17 Roccatagliata L, Vuolo L, Bonzano L, Pichiecchio A, Mancardi GL. Multiple sclerosis: Hyperintense dentate nucleus on unenhanced T1-weighted MR images is associated with the secondary progressive subtype. Radiology 2009;251:503-10.
  • 18 Kasahara S, Miki Y, Kanagaki M, Yamamoto A, Mori N, Sawada T, et al. Hyperintense Dentate Nucleus on Unenhanced T1-weighted MR Images Is Associated with a History of Brain Irradiation. Radiology 2011;258:222-8.
  • 19 Adin ME, Kleinberg L, Vaidya D, Zan E, Mirbagheri S, Yousem DM. Hyperintense Dentate Nuclei on T1-Weighted MRI: Relation to Repeat Gadolinium Administration. AJNR Am J Neuroradiol 2015;36:1859-65.
  • 20 Radbruch A, Weberling LD, Kieslich PJ, Eidel O, Burth S, Kickingereder P, et al. Gadolinium retention in the Dentate nucleus and globusPallidus is Dependent on the class of contrast agent. Radiology 2015;275:783-91.
  • 21 Kanda T, Osawa M, Oba H, Toyoda K, Kotoku J, Haruyama T, et al. High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: Association with linear versus macrocyclic gadolinium chelate administration. Radiology 2015;275:803-9.
  • 22 Cao Y, Huang DQ, Shih G, Prince MR. Signal Change in the Dentate Nucleus on T1-Weighted MR Images After Multiple Administrations of GadopentetateDimeglumine Versus Gadobutrol. AJR Am J Roentgenol 2016;206:414-9.
  • 23 Radbruch A, Weberling LD, Kieslich PJ, Hepp J, Kickingereder P, Wick W, et al. High-Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted Images: Evaluation of the Macrocyclic Gadolinium-Based Contrast Agent Invest Radiol 2015;50:805-10.
  • 24 Robert P, Violas X, Grand S, Lehericy S, Idée JM, Ballet S, et al. Linear Gadolinium-Based Contrast Agents Are Associated With Brain Gadolinium Retention in Healthy Rats. Invest Radiol 2016;51:73-82.
  • 25 Stojanov DA, Aracki-Trenkic A, Vojinovic S, Benedeto-Stojanov D, Ljubisavljevic S. Increasing signal intensity within the dentate nucleus and globuspallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: Correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol. Eur Radiol 2016;26:807-15.
  • 26 Agris J, Pietsch H, Balzer T. What Evidence Is There That Gadobutrol Causes Increasing Signal Intensity within the Dentate Nucleus and Globus Pallidus on Unenhanced T1W MRI in Patients with RRMS? Eur Radiol 2016;26:816-7.
  • 27 Ramalho J, Castillo M, AlObaidy M, Nunes RH, Ramalho M, Dale BM, et al. High Signal Intensity in Globus Pallidus and Dentate Nucleus on Unenhanced T1-weighted MR Images: Evaluation of Two Linear Gadolinium-based Contrast Agents. Radiology 2015;276:836-44.
  • 28 McDonald RJ, McDonald JS, Kallmes DF, Jentoft ME, Murray DL, Thielen KR, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology 2015;275:772-82.
  • 29 Kanda T, Fukusato T, Matsuda M, Toyoda K, Oba H, Kotoku J, et al. Gadolinium-based contrast agent accumulates in the brain even in subjects without severe renal dysfunction: Evaluation of autopsy brain specimens with inductively coupled plasma mass spectroscopy. Radiology 2015;276:228-32.
  • 30 Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J MagnReson Imaging 2009;30:1259-67.
  • 31 Amet S, Launay-Vacher V, Clément O, Frances C, Tricotel A, Stengel B, et al. Incidence of nephrogenic systemic fibrosis in patients undergoing dialysis after contrast-enhanced magnetic resonance imaging with gadolinium-based contrast agents: The Prospective Fibrose Nephrogénique Systémique study. Invest Radiol 2014;49:109-15.
  • 32 Gibby WA, Gibby KA, GibbyWA. ComparisonofGd DTPA-BMA (Omniscan) versus Gd HP-DO3A (ProHance) retention in human bone tissue by inductively coupled plasma atomic emission spectroscopy. Invest Radiol 2004;39:138-42.
  • 33 White GW, Gibby WA, Tweedle MF. ComparisonofGd (DTPABMA) (Omniscan) versus Gd (HP-DO3A) (ProHance) relative togadolinium retention in human bone tissue by inductively coupled plasma mass spectroscopy. Invest Radiol 2006;41:272-8.
  • 34 Darrah TH, Prutsman-Pfeiffer JJ, Poreda RJ, Ellen Campbell M, Hauschka PV, et al. Incorporationof excess gadolinium into human bone from medical contrast agents. Metallomics 2009;1:479-88.
  • 35 Murata N, Gonzalez-Cuyar LF, Murata K, Fligner C, Dills R, Hippe D, et al. Macrocyclic and Other Non-Group 1 Gadolinium Contrast Agents Deposit Low Levels of Gadolinium in Brain and Bone Tissue: Preliminary Results From 9 Patients With Normal Renal Function. Invest Radiol 2016;51:447-53.
  • 36 Rocklage SM, Worah D, Kim SH. Metalion release from paramagnetic chelates: What is tolerable? MagnReson Med 1991;22:216-21.
  • 37 Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J Magn Reson Imaging 2009;30:1259-67.
  • 38 Oksendal AN, Hals PA. Biodistribution and toxicity of MR imaging contrast media. J Magn Reson Imaging 1993;3:157-65.
  • 39 Pietsch H, Raschke M, Ellinger-Ziegelbauer H, Jost G, Walter J, Frenzel T, et al. The role of residual gadolinium in the induction of nephrogenic systemic fibrosis-like skin lesions in rats. Invest Radiol 2011;46:48-56.
  • 40 Ogi S, Fukumitsu N, Tsuchida D, Uchiyama M, Mori Y, Matsui K. Imaging of bilateral striopallidodentate calcinosis. Clin Nucl Med 2002;27:721-4.
  • 41 Roman-Goldstein SM, Barnett PA, McCormick CI, Ball MJ, Ramsey F, Neuwelt EA. Effects of gadopentetatedimeglumine administration after osmotic blood brain barrier disruption: Toxicity and MR imaging findings. AJNR Am J Neuroradiol 1991;12:885-90.
  • 42 Available from: https://www2.rsna.org/timssnet/media/pressreleases/PDF/pressreleasePDF.cfm?ID=810 [Last accessed on 2015 May 05].
  • 43 Available from: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm456012.htm [Last accessed on 2015 Jul 27].