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Home ›› About Speciation ›› Speciation News

The retention of gadolinium in the human body following the use of gadolinium-based MRI contrast agents: a call to action for analytical chemists

(20.02.2019)

Gd-based contrast agends partly remain in the body of patients for quite some time. The information from speciation analysis is needed in order to answer why.

Background:

Gd-based MRI contrast agents are considered essential for modern medical diagnostic imaging leading to about 25 Mio applications per year. While most of the administered Gd (5-10 millimoles) is rapidly excreted via urine during the first few days following application, a small part is retained in different organs including liver, kidney, brain and bones for much longer time. While prolonged residence time was first observed for patients with reduced kidney function, it is meanwhile established that such retention also occurs in patients with normal kidney function. While retention of Gd in patients with advanced kidney disease can be related to nephrogenic systemic fibrosis (NSF), up to now retention in patients with normal kidney function could not be related to such pathology. Anyhow, regulatory agiencies have restricted the use of specific GBCA and have called manufactureres and researchers to present data on the biological effects of such retention.

The new publication:

Researchers from the Massachusetts General Hospital and Harvard Medical School have now compiled all the obervations regarding the Gd retention. From these obervations it is clear that not all of the injected dose of GBCA is eliminated.

However many questions remain:

What part of the injected dose remains in the body after a week, month or year ?
In what tissue does the Gd retain ?
In what form is the Gd retained ?
What is the reason for retention ?
Is the retention being different for the different types of GBCA?
What are the long-term effects?

The authors conclude that specialized expertise that exists in the bioinorganic and bioanalytical chemistry communities is needed to answer these questions and they express their hope that their review will stimulate this community to tackle these problems.

They also list the different techniques that could help to answer the open questions. These are the well known techniques within the tool-box for speciation analysis.

The cited study:

Mariane Le Fur, Peter Caravan, The biological fate of gadolinium-based MRI contrast agents: a call to action for bioinorganic chemists, Metallomics, 11(2 (2019) 240-254. DOI: 10.1039/c8mt00302e

Related studies (newest first):

Nathalie Fretellier, Agnès Granottier, Marlène Rasschaert, Anne-Laure Grindel, Fannie Baudimont, Philippe Robert, Jean-Marc Idée, Claire Corot, Does Age Interfere With Gadolinium Toxicity and Presence in Brain and Bone Tissues?A Comparative Gadoterate Versus Gadodiamide Study in Juvenile and Adult Rats, Invest. Radiol., 54/2 (2019) 61-71. DOI: 10.1097/RLI.0000000000000517

Stefanie Fingerhut, Michael Sperling, Markus Holling, Thomas Niederstadt, Thomas Allkemper, Alexander Radbruch, Walter Heindel, Werner Paulus, Astrid Jeibmann, Uwe Karst, Gadolinium‑based contrast agents induce gadolinium deposits in cerebral vessel walls, while the neuropil is not affected: an autopsy study, Acta Neuropathol., 136 (2018) 127-138. DOI: 10.1007/s00401-018-1857-4

S. Fingerhut, A.C. Niehoff, M. Sperling, A. Jeibmann, W. Paulus, T. Niederstadt, T. Allkemper, W. Heindel, M. Holling, U. Karst, Spatially resolved quantification of gadolinium deposited in the brain of a patient treated with gadolinium-based contrast agents. J. Trace Elem. Med. Biol., 45 (2018) 125–130. DOI: 10.1016/j.jtemb.2017.10.004

T. Frenzel, C. Apte, G. Jost, L. Schockel, J. Lohrke, H. Pietsch, Quantification and assess-ment of the chemical form of residualgadolinium in the brain after repeated administration of gadolinium-based contrast agents comparative study in rats. Invest. Radiol., 52 (2017) 396–404. DOI: 10.1097/Rli.0000000000000352

G. Jost, T. Frenzel, J. Lohrke, D.C. Lenhard, S. Naganawa, H. Pietsch, Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue. Eur. Radiol., 27 (2017) 2877–2885.

DOI: 10.1007/s00330-016-4654-2

J. Lohrke, A.L. Frisk, T. Frenzel, L. Schöckel, M. Rosenbruch, G. Jost, D.C. Lenhard, M.A. Sieber, V. Nischwitz, A. Küppers, H. Pietsch, Histology and gadolinium distribution in the rodent brain after the administration of cumulative high doses of linear and macrocyclic gadolinium-based contrast agents. Invest. Radiol., 52 (2017) 324–333. DOI: 10.1097/Rli.0000000000000344

Marvin Birka, Kristina S. Wentker, Elke Lusmöller, Brigit Arheilger, Christoph Alexander Wehe, Michael Sperling, Rudolf Stadler, and Uwe Karst, Diagnosis of Nephrogenic Systemic Fibrosis by means of Elemental Bioimaging and Speciation Analysis, Anal. Chem., 87/6 (2015) 3321-3328. DOI: 10.1021/ac504488k

Lena Telgmann, Helene Faber, Sandra Jahn, Daniel Melles, Hannah Simon, Michael Sperling, Uwe Karst, Identification and quantification of potential metabolites of Gd-based contrast agents by electrochemistry/separations/mass spectrometry, J. Chromatography A, 1240 (2012) 147- 155. doi: 10.1016/j.chroma.2012.03.088

Charu Thakral, Jerrold L. Abraham, Gadolinium-Induced Nephrogenic Systemic Fibrosis Is Associated with Insoluble Gd Deposits in Tissues: In Vivo Transmetallation Confirmed by Microanalysis, J. Cutan Pathol., 36 (2009) 1244–1254. doi: 10.1111/j.1600-0560.2009.01283.x

Thomas H. Darrah, Jennifer J. Prutsman-Pfeiffer, Robert J. Poreda, M. Ellen Campbell, Peter V. Hauschka, Robyn E. Hannigan, Incorporation of excess gadolinium into human bone from medical contrast agents, Metallomics, /6 (2009) 479–488, DOI: 10.1039/b905145g

W.A. High, R.A. Ayers, J. Chandler, G. Zito, S.E. Cowper, Gadolinium is detectable within the tissue of patients with nephrogenic systemic fibrosis, J. Am. Acad. Dermatol., 56 (2007) 21–26. DOI: 10.1016/j.jaad.2006.10.047

Gregory W. White, Wendell A. Gibby, Michael F. Tweedle, 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., 41/3 (2006) 272-278. doi: 10.1097/01.rli.0000186569.32408.95

Wendell A. Gibby, Krissa A. Gibby, W. Andrew Gibby, 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., 39/3 (2004) 138-142. doi: 10.1097/01.rli.0000112789.57341.01