Gadolinium Concentrations in Biological Matrices From Patients Exposed to Gadolinium-Based Contrast Agents.

Szczegóły
Abstrakt

Tytuł:: Gadolinium Concentrations in Biological Matrices From Patients Exposed to Gadolinium-Based Contrast Agents.
Autorzy:: Layne KA; From the Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust.
Raja K; Viapath Analytics, King's College Hospital NHS Foundation Trust.
Dargan PI
Wood DM
Źródło:: Investigative radiology [Invest Radiol] 2021 Jul 01; Vol. 56 (7), pp. 458-464.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: 1998- : Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: Philadelphia.
MeSH Terms:: Gadolinium*
Organometallic Compounds*
Contrast Media/adverse effects ; Gadolinium DTPA ; Humans ; Magnetic Resonance Imaging
References:: Lohrke J, Frenzel T, Endrikat J, et al. 25 years of contrast-enhanced MRI: developments, current challenges and future perspectives. Adv Ther . 2016;33:1–28.
Wagner B, Drel V, Gorin Y. Pathophysiology of gadolinium-associated systemic fibrosis. Am J Physiol Renal Physiol . 2016;311:F1–F11.
Grobner T. Gadolinium—a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant . 2006;21:1104–1108.
Boyd AS, Zic JA, Abraham JL. Gadolinium deposition in nephrogenic fibrosing dermopathy. J Am Acad Dermatol . 2007;56:27–30.
Schieda N, Blaichman JI, Costa AF, et al. Gadolinium-based contrast agents in kidney disease: a comprehensive review and clinical practice guideline issued by the Canadian Association of Radiologists. Can J Kidney Health Dis . 2018;5:2054358118778573.
Edwards BJ, Laumann AE, Nardone B, et al. Advancing pharmacovigilance through academic-legal collaboration: the case of gadolinium-based contrast agents and nephrogenic systemic fibrosis-a Research on Adverse Drug Events and Reports (RADAR) report. Br J Radiol . 2014;87:20140307.
Thomsen HS. Nephrogenic systemic fibrosis: a serious late adverse reaction to gadodiamide. Eur Radiol . 2006;16:2619–2621.
Layne KA, Dargan PI, Archer JRH, et al. Gadolinium deposition and the potential for toxicological sequelae—a literature review of issues surrounding gadolinium-based contrast agents. Br J Clin Pharmacol . 2018;84:2522–2534.
Alwasiyah D, Murphy C, Jannetto P, et al. Urinary gadolinium levels after contrast-enhanced MRI in individuals with normal renal function: a pilot study. J Med Toxicol . 2019;15:121–127.
Oksendal AN, Hals PA. Biodistribution and toxicity of MR imaging contrast media. J Magn Reson Imaging . 1993;3:157–165.
Hao D, Ai T, Goerner F, et al. MRI contrast agents: basic chemistry and safety. J Magn Reson Imaging . 2012;36:1060–1071.
White GW, Gibby WA, Tweedle MF. 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 . 2006;41:272–278.
McDonald RJ, McDonald JS, Kallmes DF, et al. Gadolinium deposition in human brain tissues after contrast-enhanced MR imaging in adult patients without intracranial abnormalities. Radiology . 2017;285:546–554.
Layne KA, Wood DM, Dargan PI. Gadolinium-based contrast agents—what is the evidence for 'gadolinium deposition disease’ and the use of chelation therapy? Clin Toxicol (Phila) . 2020;58:151–160.
Semelka RC, Commander CW, Jay M, et al. Presumed gadolinium toxicity in subjects with normal renal function: a report of 4 cases. Invest Radiol . 2016;51:661–665.
Nehra AK, McDonald RJ, Bluhm AM, et al. Accumulation of gadolinium in human cerebrospinal fluid after gadobutrol-enhanced MR imaging: a prospective observational cohort study. Radiology . 2018;288:416–423.
Semelka RC, Ramalho J, Vakharia A, et al. Gadolinium deposition disease: initial description of a disease that has been around for a while. Magn Reson Imaging . 2016;34:1383–1390.
Layne KA, Wood DM, Dixon-Zegeye M, et al. Establishing reference intervals for gadolinium concentrations in blood, plasma, and urine in individuals not previously exposed to gadolinium-based contrast agents. Invest Radiol . 2020;55:405–411.
Maecker HT, Wang W, Rosenberg-Hasson Y, et al. An initial investigation of serum cytokine levels in patients with gadolinium retention. Radiol Bras . 2020;53:306–313.
Lattanzio SM, Imbesi F. Fibromyalgia associated with repeated gadolinium contrast-enhanced MRI examinations. Radiol Case Rep . 2020;15:534–541.
Bellato E, Marini E, Castoldi F, et al. Fibromyalgia syndrome: etiology, pathogenesis, diagnosis, and treatment. Pain Res Treat . 2012;2012:426130.
Furness PJ, Vogt K, Ashe S, et al. What causes fibromyalgia? An online survey of patient perspectives. Health Psychol Open . 2018;5:2055102918802683.
Bradley LA. Pathophysiology of fibromyalgia. Am J Med . 2009;122(suppl 12):S22–S30.
McDonald RJ, McDonald JS, Kallmes DF, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology . 2015;275:772–782.
Kanda T, Fukusato T, Matsuda M, 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;276:228–232.
Murata N, Gonzalez-Cuyar LF, Murata K, 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;51:447–453.
Nelson S, Toma H, LaMonica H, et al. Major cognitive changes and micrographia following globus pallidus infarct. Case Rep Neurol Med . 2014;2014:252486.
Koide R, Bandoh M. Patient with globus pallidus infarction presenting with reversible dementia. J Neuropsychiatry Clin Neurosci . 2013;25:E41–E42.
Sultan F, Hamodeh S, Baizer JS. The human dentate nucleus: a complex shape untangled. Neuroscience . 2010;167:965–968.
Gathings RM, Reddy R, Santa Cruz D, et al. Gadolinium-associated plaques: a new, distinctive clinical entity. JAMA Dermatol . 2015;151:316–319.
Roberts DR, Lindhorst SM, Welsh CT, et al. High levels of gadolinium deposition in the skin of a patient with normal renal function. Invest Radiol . 2016;51:280–289.
McLean RM. Measuring population sodium intake: a review of methods. Nutrients . 2014;6:4651–4662.
Boyken J, Frenzel T, Lohrke J, et al. Impact of treatment with chelating agents depends on the stability of administered GBCAs: a comparative study in rats. Invest Radiol . 2019;54:76–82.
US Food and Drug Administration—Drug Safety Communications. Available at: https://www.fda.gov/media/109825/download . Accessed May 2020.
Frenzel T, Lengsfeld P, Schirmer H, et al. Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37 degrees C. Invest Radiol . 2008;43:817–828.
Le Mignon MM, Chambon C, Warrington S, et al. Gd-DOTA. Pharmacokinetics and tolerability after intravenous injection into healthy volunteers. Invest Radiol . 1990;25:933–937.
Staks T, Schuhmann-Giampieri G, Frenzel T, et al. Pharmacokinetics, dose proportionality, and tolerability of gadobutrol after single intravenous injection in healthy volunteers. Invest Radiol . 1994;29:709–715.
Harpur ES, Worah D, Hals PA, et al. Preclinical safety assessment and pharmacokinetics of gadodiamide injection, a new magnetic resonance imaging contrast agent. Invest Radiol . 1993;28(suppl 1):S28–S43.
Van Wagoner M, Worah D. Gadodiamide injection. First human experience with the nonionic magnetic resonance imaging enhancement agent. Invest Radiol . 1993;28(suppl 1):S44–S48.
Xia D, Davis RL, Crawford JA, et al. Gadolinium released from MR contrast agents is deposited in brain tumors: in situ demonstration using scanning electron microscopy with energy dispersive X-ray spectroscopy. Acta Radiol . 2010;51:1126–1136.
Errante Y, Cirimele V, Mallio CA, et al. 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;49:685–690.
Kanda T, Ishii K, Kawaguchi H, et al. 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 . 2014;270:834–841.
Kanda T, Osawa M, Oba H, et al. High signal intensity in dentate nucleus on unenhanced T1-weighted MR images: association with linear versus macrocyclic gadolinium chelate administration. Radiology . 2015;275:803–809.
Stojanov DA, Aracki-Trenkic A, Vojinovic S, et al. Increasing signal intensity within the dentate nucleus and globus pallidus 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;26:807–815.
DeBevits JJ 4th, Munbodh R, Bageac D, et al. Gray matter nucleus hyperintensity after monthly triple-dose gadopentetate dimeglumine with long-term magnetic resonance imaging. Invest Radiol . 2020;55:629–635.
Strzeminska I, Factor C, Robert P, et al. Long-term evaluation of gadolinium retention in rat brain after single injection of a clinically relevant dose of gadolinium-based contrast agents. Invest Radiol . 2020;55:138–143.
Wang S, Hesse B, Roman M, et al. Increased retention of gadolinium in the inflamed brain after repeated administration of gadopentetate dimeglumine: a proof-of-concept study in mice combining ICP-MS and micro- and nano-SR-XRF. Invest Radiol . 2019;54:617–626.
European Medicines Agency—Pharmacovigilance Risk Assessment Committee statement on the use of linear gadolinium agents. Available at: https://www.ema.europa.eu/en/documents/referral/gadolinium-article-31-referral-prac-confirms-restrictions-use-linear-gadolinium-agents_en.pdf . Accessed May 2020.
GOV.UK Drug Safety Update. Available at: https://www.gov.uk/drug-safety-update/gadolinium-containing-contrast-agents-omniscan-and-iv-magnevist-no-longer-authorised-multihance-and-primovist-for-use-only-in-liver-imaging . Accessed May 2020.
Substance Nomenclature:: 0 (Contrast Media)
0 (Organometallic Compounds)
AU0V1LM3JT (Gadolinium)
K2I13DR72L (Gadolinium DTPA)
Entry Date(s):: Date Created: 20210604 Date Completed: 20211015 Latest Revision: 20230926
Update Code:: 20240105
DOI:: 10.1097/RLI.0000000000000762
PMID:: 34086014
: Czasopismo naukowe

Objectives: There is increasing evidence that Gd may be retained within the skin, bones, and solid organs in patients with normal renal function after exposure to Gd-based contrast agents (GBCAs). Here we present clinical data from 19 patients who requested referral to our clinical toxicology service for assessment of potential "Gd toxicity."
Materials and Methods: Patients had undergone a median of 2 (interquartile range [IQR], 1-5) exposures to GBCAs and were reviewed at a median of 5 months (IQR, 2-8 months) after the last GBCA exposure. Patients had a clinical assessment by a clinical toxicologist, and biological samples were taken in 17 patients (89.5%). Gd concentrations were measured in these samples using inductively coupled plasma mass spectrometry.
Results: All patients had significant comorbidities, and after an extensive clinical review, none of the reported symptoms were considered likely to be related to "Gd toxicity." Whole blood, plasma, and urine samples had detectable Gd concentrations in 69.2%, 78.6%, and 95.2% of samples, respectively. Median (IQR) concentrations of Gd were as follows: whole blood, 0.013 ng/mL (IQR, limit of detection [LOD]-0.884 ng/mL); plasma, 0.012 ng/mL (IQR, LOD-0.046 ng/mL); and spot urine, 0.304 μg/g creatinine (IQR, 0.070-3.702 μg/g creatinine). There were positive correlations between whole blood and plasma (P = 0.0024, r = 0.84), whole blood and urine (P = 0.0018, r = 0.82), and plasma and urine (P = 0.0001, r = 0.89) Gd concentrations. There was a negative correlation between Gd concentrations and the period after exposure for whole blood (P = 0.0028, r = -0.80), plasma (P = 0.0004, r = -0.86), and urine (P < 0.0001, r = -0.91).
Conclusions: We identified detectable Gd concentrations in biological matrices from all patients reporting exposure to GBCAs who were reviewed in our clinical toxicology outpatient clinic with concerns regarding potential "Gd toxicity"; however, there were no clinical features of toxicity present in this cohort. Further research is required to explore the pharmacokinetics and pharmacodynamics of GBCAs in patients with normal renal function and to determine the clinical significance of these detectable Gd concentrations.
Competing Interests: Conflicts of interest and sources of funding: none declared.
(Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Informacja