The Macrocyclic Gadolinium-Based Contrast Agents Gadobutrol and Gadoteridol Show Similar Elimination Kinetics From the Brain After Repeated Intravenous Injections in Rabbits.
Journal
Investigative radiology
ISSN: 1536-0210
Titre abrégé: Invest Radiol
Pays: United States
ID NLM: 0045377
Informations de publication
Date de publication:
01 06 2021
01 06 2021
Historique:
pubmed:
2
12
2020
medline:
16
10
2021
entrez:
1
12
2020
Statut:
ppublish
Résumé
Male white New Zealand rabbits (2.4-3.1 kg) in 2 study groups (n = 21 each) received 3 injections of either gadobutrol or gadoteridol at 0.9 mmol Gd/kg within 5 days (total dose, 2.7 mmol Gd/kg). Animals in one control group (n = 9) received 3 injections of saline (1.8 mL/kg). After 2, 6, and 12 weeks, 7 animals from each study group and 3 from the control group were killed and the Gd concentrations in the cerebellum, cerebrum, in blood and in urine were determined by inductively coupled plasma mass spectrometry. The chemical species of excreted Gd in urine were determined by high pressure liquid chromatography. No significant (P > 0.05) differences in the Gd concentrations in the brain of rabbits were observed between the 2 macrocyclic GBCAs gadoteridol and gadobutrol at all time points. In the gadobutrol group, the mean Gd concentrations in the cerebellum and cerebrum decreased from 0.26 and 0.21 nmol Gd/g after 2 weeks, to 0.040 and 0.027 nmol Gd/g after 12 weeks, respectively, and in the gadoteridol group, from 0.25 and 0.21, to 0.037 and 0.023 nmol Gd/g, respectively. The plasma levels decreased from 0.11 and 0.13 nmol Gd/mL at 2 weeks for gadobutrol and gadoteridol to below the limit of quantification (<0.005 nmol Gd/mL) at 12 weeks. The urine concentration dropped in a biphasic course from 2 to 6 and from 6 to 12 weeks for both agents. The Gd excreted after 12 weeks was still present in the urine in the chemical form of the intact Gd complex for both agents. Contrary to what had been reported in rats, no significant differences in the elimination kinetics from brain tissue in rabbits were observed after intravenous injection of multiple doses of the macrocyclic GBCAs gadobutrol and gadoteridol.
Identifiants
pubmed: 33259443
pii: 00004424-202106000-00001
doi: 10.1097/RLI.0000000000000749
doi:
Substances chimiques
Contrast Media
0
Heterocyclic Compounds
0
Organometallic Compounds
0
gadoteridol
0199MV609F
gadobutrol
1BJ477IO2L
Gadolinium
AU0V1LM3JT
Gadolinium DTPA
K2I13DR72L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
341-347Informations de copyright
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of interest and sources of funding: all authors are employees of Bayer AG.
Références
Berry I, Ranjeva JP, Clanet M, et al. Central nervous system. In: Thomsen HS, Muller RN, Mattrey RF, eds. Trends in Contrast Media . Heidelberg, Germany: Springer; 1999:195–218.
Montagne A, Toga AW, Zlokovic BV. Blood-brain barrier permeability and gadolinium: benefits and potential pitfalls in research. JAMA Neurol . 2016;73:13–14.
Aime S, Caravan P. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J Magn Reson Imaging . 2009;30:1259–1267.
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.
Choi JW, Moon W-J. Gadolinium deposition in the brain: current updates. Korean J Radiol . 2019;20:134–147.
Jost G, Frenzel T, Lohrke J, et al. 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 . 2017;27:2877–2885.
Ohashi T, Naganawa S, Ogawa E, et al. Signal intensity of the cerebrospinal fluid after intravenous administration of gadolinium-based contrast agents: strong contrast enhancement around the vein of Labbe. Magn Reson Med Sci . 2019;18:194–199.
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.
Berger F, Kubik-Huch RA, Niemann T, et al. Gadolinium distribution in cerebrospinal fluid after administration of a gadolinium-based MR contrast agent in humans. Radiology . 2018;288:703–709.
Robert P, Frenzel T, Factor C, et al. Methodological aspects for preclinical evaluation of gadolinium presence in brain tissue: critical appraisal and suggestions for harmonization—a joint initiative. Invest Radiol . 2018;53:499–517.
Runge VM. Safety of the gadolinium-based contrast agents for magnetic resonance imaging, focusing in part on their accumulation in the brain and especially the dentate nucleus. Invest Radiol . 2016;51:273–279.
Tweedle MF, Wedeking P, Kumar K. Biodistribution of radiolabeled, formulated gadopentetate, gadoteridol, gadoterate, and gadodiamide in mice and rats. Invest Radiol . 1995;30:372–380.
Jost G, Frenzel T, Boyken J, et al. Long-term excretion of gadolinium-based contrast agents: linear versus macrocyclic agents in an experimental rat model. Radiology . 2019;290:340–348.
Robert P, Fingerhut S, Factor C, et al. One-year retention of gadolinium in the brain: comparison of gadodiamide and gadoterate meglumine in a rodent model. Radiology . 2018;288:424–433.
McDonald RJ, McDonald JS, Dai D, et al. Comparison of gadolinium concentrations within multiple rat organs after intravenous administration of linear versus macrocyclic gadolinium chelates. Radiology . 2017;285:536–545.
Bussi S, Coppo A, Botteron C, et al. Differences in gadolinium retention after repeated injections of macrocyclic MR contrast agents to rats. J Magn Reson Imaging . 2018;47:746–752.
Bussi S, Coppo A, Celeste R, et al. Macrocyclic MR contrast agents: evaluation of multiple-organ gadolinium retention in healthy rats. Insights Imaging . 2020;11:11.
FDA: U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for Industry: Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. 2005. Available at: https://www.fda.gov/downloads/drugs/guidances/ucm078932.pdf . Accessed August 25, 2020.
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.
Bornhorst J, Wegwerth P, Day P, et al. Urinary reference intervals for gadolinium in individuals without recent exposure to gadolinium-based contrast agents. Clin Chem Lab Med . 2020;58:e87–e90.
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.
SAS® Institute Inc. SAS/STAT® [Computer Program] 14.2 User's Guide . Cary, NC: SAS® Institute Inc; 2016.
Lohrke J, Frisk AL, Frenzel T, et al. 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 . 2017;52:324–333.
Knobloch G, Frenzel T, Pietsch H, et al. Signal enhancement and enhancement kinetics of gadobutrol, gadoteridol, and gadoterate meglumine in various body regions: a comparative animal study. Invest Radiol . 2020;55:367–373.
Radbruch A, Richter H, Fingerhut S, et al. Gadolinium deposition in the brain in a large animal model: comparison of linear and macrocyclic gadolinium-based contrast agents. Invest Radiol . 2019;54:531–536.
McDonald RJ, McDonald JS, Kallmes DF, et al. Intracranial gadolinium deposition after contrast-enhanced MR imaging. Radiology . 2015;275:772–782.
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.
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;51:447–553.
Stanescu AL, Shaw DW, Murata N, et al. Brain tissue gadolinium retention in pediatric patients after contrast-enhanced magnetic resonance exams: pathological confirmation. Pediatr Radiol . 2020;50:388–396.
Idee J-M, Robert P, Raynaud J-S, et al. Region of interest selection in nonclinical studies of accumulated gadolinium-based contrast agent-induced T1 hyperintensity in deep cerebellar nuclei. Radiology . 2018;287:360–362.
Eakins MN, Eaton SM, Fisco RA, et al. Physicochemical properties, pharmacokinetics, and biodistribution of gadoteridol injection in rats and dogs. Acad Radiol . 1995;2:584–591.
Weinmann H, Platzek J, Radüchel B, et al. A new macrocyclic gadolinium chelate as a contrast agent for MRI. Eur Radiol . 1993;3(suppl):126.
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.
McLachlan SJ, Eaton S, De Simone DN. Pharmacokinetic behavior of gadoteridol injection. Invest Radiol . 1992;27:S12–S15.
Lancelot E. Revisiting the pharmacokinetic profiles of gadolinium-based contrast agents: differences in long-term biodistribution and excretion. Invest Radiol . 2016;51:691–700.
Birka M, Wentker KS, Lusmoller E, et al. Diagnosis of nephrogenic systemic fibrosis by means of elemental bioimaging and speciation analysis. Anal Chem . 2015;87:3321–3328.
Taoka T, Naganawa S. Gadolinium-based contrast media, cerebrospinal fluid and the glymphatic system: possible mechanisms for the deposition of gadolinium in the brain. Magn Reson Med Sci . 2018;17:111–119.
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.
Frenzel T, Apte C, Jost G, et al. Quantification and assessment of the chemical form of residual gadolinium in the brain after repeated administration of gadolinium-based contrast agents: comparative study in rats. Invest Radiol . 2017;52:396–404.