{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:40:59Z","timestamp":1791927659863,"version":"4.3.4"},"reference-count":56,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Gadolinium (Gd) is one of the rare-earth elements. The properties of its trivalent cation (Gd3+) make it suitable to serve as the central ion in chelates administered intravenously to patients as a contrast agent in magnetic resonance imaging. Such Gd-chelates have been used for more than thirty years. During the past decades, knowledge has increased about potential harmful effects of Gd-chelates in patients with severe renal dysfunction. In such patients, there is a risk for a potentially disabling and lethal disease, nephrogenic systemic fibrosis. Restricting the use of Gd-chelates in persons with severely impaired renal function has decreased the occurrence of this toxic effect in the last decade. There has also been an increasing awareness of Gd-retention in the body, even in patients without renal dysfunction. The cumulative number of doses given, and the chemical structure of the chelate given, are factors of importance for retention in tissues. This review describes the chemical properties of Gd and its medically used chelates, as well as its toxicity and potential side effects related to injection of Gd-chelates.<\/jats:p>","DOI":"10.3390\/biom12060742","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T22:04:06Z","timestamp":1653429846000},"page":"742","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Gadolinium in Medical Imaging\u2014Usefulness, Toxic Reactions and Possible Countermeasures\u2014A Review"],"prefix":"10.3390","volume":"12","author":[{"given":"Lennart","family":"Blomqvist","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-17176 Stockholm, Sweden"},{"name":"Department of Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, SE-17176 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6938-7053","authenticated-orcid":false,"given":"Gunnar F.","family":"Nordberg","sequence":"additional","affiliation":[{"name":"Division of Sustainable Health, Department of Public Health and Clinical Medicine, Ume\u00e5 University, SE-90187 Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4004-1988","authenticated-orcid":false,"given":"Valeria M.","family":"Nurchi","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, University of Cagliari, 09042 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7518-5703","authenticated-orcid":false,"given":"Jan O.","family":"Aaseth","sequence":"additional","affiliation":[{"name":"Department of Research, Innlandet Hospital Trust, P.O. Box 104, N-2381 Brumunddal, Norway"},{"name":"Faculty of Health and Social Sciences, Inland Norway University of Applied Sciences, N-2418 Elverum, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.progpolymsci.2012.07.001","article-title":"Macromolecular MRI contrast agents: Structures, properties and applications","volume":"38","author":"Tang","year":"2012","journal-title":"Prog. Polym. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1021\/cr980440x","article-title":"Gadolinium(III) chelates as MRI contrast agents: Structure, dynamics and applications","volume":"99","author":"Caravan","year":"1999","journal-title":"Chem. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1021\/acs.chemrev.8b00363","article-title":"Chemistry of MRI Contrast Agensts: Current Challenges and New frontiers","volume":"119","author":"Wahsner","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"561","DOI":"10.34067\/KID.0000272019","article-title":"Gadolinium-Based Contrast Agent Use, Their Safety, and Practice Evolution","volume":"1","author":"Do","year":"2020","journal-title":"Kidney360"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s10534-016-9931-7","article-title":"Gadolinium-based contrast agent toxicity: A review of known and proposed mechanisms","volume":"29","author":"Rogosnitzky","year":"2016","journal-title":"BioMetals"},{"key":"ref_6","unstructured":"Cowling, T., and Frey, N. (2019). Macrocyclic and linear gadolinium based contrast agents for adults undergoing magnetic resonance imaging: A review of safety, CADTH Rapid Response Reports."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cbpa.2018.04.006","article-title":"Advances in gadolinium-based MRI contrast agent designs for monitoring biological processes in vivo","volume":"45","author":"Lux","year":"2018","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ejrad.2008.01.023","article-title":"Extracellular gadolinium-based contrast media: Differences in diagnostic efficacy","volume":"66","author":"Bellin","year":"2008","journal-title":"Eur. J. Radiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1097\/RLI.0000000000000352","article-title":"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","volume":"52","author":"Frenzel","year":"2017","journal-title":"Investig. Radiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1148\/radiol.2020200073","article-title":"Adverse Events to the Gadolinium-based Contrast Agent Gadoxetic Acid: Systematic Review and Meta-Analysis","volume":"297","author":"Schieda","year":"2020","journal-title":"Radiology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1097\/01.rli.0000074585.46615.2e","article-title":"Gadobenate Dimeglumine-Enhanced Magnetic Resonance Angiography of the Pelvic Arteries","volume":"38","author":"Wasser","year":"2003","journal-title":"Investig. Radiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.rcl.2005.01.004","article-title":"Shoulder MR Arthrography: How, Why, When","volume":"43","author":"Jbara","year":"2005","journal-title":"Radiol. Clin. North. Am."},{"key":"ref_13","first-page":"395","article-title":"Comparison of the biodistribution of 153Gd-labeled Gd(DTPA)2\u2212, Gd(DOTA)\u2212, and Gd(acetate) in in mice","volume":"15","author":"Wedeking","year":"1988","journal-title":"Nucl. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0730-725X(87)90023-3","article-title":"Biodistribution of GdCl3 and Gd-DTPA and their influence on proton magnetic relaxation in rat tissues","volume":"5","author":"Barnhart","year":"1987","journal-title":"Magn. Reson. Imaging"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/cmmi.100","article-title":"Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents","volume":"1","author":"Laurent","year":"2006","journal-title":"Contrast Media Mol. Imaging"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1111\/bcp.13718","article-title":"Gadolinium deposition and the potential for toxicological sequelae\u2014A literature review of issues surrounding gadolinium-based contrast agents","volume":"84","author":"Layne","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1148\/radiol.13131669","article-title":"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","volume":"270","author":"Kanda","year":"2014","journal-title":"Radiology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5567","DOI":"10.1039\/C9NA00567F","article-title":"Formation of gadolinium\u2013ferritin from clinical magnetic resonance contrast agents","volume":"2","author":"Neburkova","year":"2020","journal-title":"Nanoscale Adv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.3109\/02841851.2010.515614","article-title":"Gadolinium released from MR contrast agents is deposited in brain tumors: In situ demonstration using scanning electron microscopy with energy dispersive X-ray spectroscopy","volume":"51","author":"Xia","year":"2010","journal-title":"Acta Radiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1148\/radiol.2015150337","article-title":"Gadolinium Retention in the Dentate Nucleus and Globus Pallidus Is Dependent on the Class of Contrast Agent","volume":"275","author":"Radbruch","year":"2015","journal-title":"Radiology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1097\/RLI.0b013e3181852171","article-title":"Stability of Gadolinium-Based Magnetic Resonance Imaging Contrast Agents in Human Serum at 37 \u00b0C","volume":"43","author":"Frenzel","year":"2008","journal-title":"Investig. Radiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1097\/00004424-200102000-00008","article-title":"Stability of MRI Paramagnetic Contrast Media A Proton Relaxometric Protocol for Transmetallation Assessment","volume":"36","author":"Laurent","year":"2001","journal-title":"Investig. Radiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/0730-725X(91)90429-P","article-title":"Reaction of gadolinium chelates with endogenously available ions","volume":"9","author":"Tweedle","year":"1991","journal-title":"Magn. Reson. Imaging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1002\/jmri.21966","article-title":"Primer on gadolinium chemistry","volume":"30","author":"Sherry","year":"2009","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1177\/019262339702500301","article-title":"Gadolinium Chloride Toxicity in the Rat","volume":"25","author":"Spencer","year":"1997","journal-title":"Toxicol. Pathol."},{"key":"ref_26","first-page":"933","article-title":"Gd-DOTA. Pharmacokinetics and tolerability after intravenous injection into healthy volunteers","volume":"25","author":"Chambon","year":"1990","journal-title":"Investig. Radiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1097\/RLI.0000000000000467","article-title":"Methodological Aspects for Preclinical Evaluation of Gadolinium Presence in Brain Tissue Critical Appraisal and Suggestions for Harmonization-A Joint Initiative","volume":"53","author":"Robert","year":"2018","journal-title":"Investig. Radiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1148\/radiol.2021211349","article-title":"Symptoms Associated with Gadolinium Exposure (SAGE): A Suggested Term","volume":"302","author":"McDonald","year":"2022","journal-title":"Radiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/ACI.0000000000000371","article-title":"Hypersensitivity reactions to gadolinium-based contrast agents","volume":"17","author":"Fok","year":"2017","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_30","first-page":"100990","article-title":"Late-onset acute respiratory distress syndrome induced by a gadolinium-based contrast agent","volume":"29","author":"Kato","year":"2019","journal-title":"Respir. Med. Case Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1007\/s00330-002-1628-3","article-title":"Members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR)). Gadolinium-containing contrast media for radiographic examinations: A position paper","volume":"12","author":"Thomsen","year":"2002","journal-title":"Eur. Radiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1007\/s00330-011-2225-0","article-title":"Contrast induced nephropathy: Updated ESUR Contrast Media Safety Committee guidelines","volume":"21","author":"Stacul","year":"2011","journal-title":"Eur. Radiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1111\/j.1365-2133.2010.09918.x","article-title":"Synchrotron X-ray analyses demonstrate phosphate-bound gadolinium in skin in nephrogenic systemic fibrosis","volume":"163","author":"George","year":"2010","journal-title":"Br. J. Dermatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1039\/C8MT00302E","article-title":"The biological fate of gadolinium-based MRI contrast agents: A call to action for bioinorganic chemists","volume":"11","author":"Caravan","year":"2019","journal-title":"Metallomics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1148\/radiol.2020202903","article-title":"Use of Intravenous Gadolinium-based Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation","volume":"298","author":"Weinreb","year":"2021","journal-title":"Radiology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1148\/rg.2020190110","article-title":"Gadolinium Deposition and Nephrogenic Systemic Fibrosis: A Radiologist\u2019s Primer","volume":"40","author":"Mathur","year":"2020","journal-title":"RadioGraphics"},{"key":"ref_37","unstructured":"EMA (2017). EMA\u2019s Final Opinion Confirms Restrictions on Use of Linear Gadolinium Agents in Body Scans EMA\/457616\/2017, European Medicines Agency."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1148\/radiol.2018181151","article-title":"Gadolinium Retention: A Research Roadmap from the 2018 NIH\/ACR\/RSNA Workshop on Gadolinium Chelates","volume":"289","author":"McDonald","year":"2018","journal-title":"Radiology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S1474-4422(17)30158-8","article-title":"Gadolinium deposition in the brain: Summary of evidence and recommendations","volume":"16","author":"Gulani","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3389\/fnmol.2018.00335","article-title":"Gadolinium Deposition in Brain: Current Scientific Evidence and Future Perspectives","volume":"11","author":"Guo","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1097\/RLI.0000000000000417","article-title":"The Effect of Perinatal Gadolinium-Based Contrast Agents on Adult Mice Behavior","volume":"53","author":"Khairinisa","year":"2018","journal-title":"Investig. Radiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1002\/jmri.26317","article-title":"MRI in pregnancy: Indications and practical considerations","volume":"49","author":"Mervak","year":"2019","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1148\/radiol.15141488","article-title":"Gadolinium Chelate Contrast Material in Pregnancy: Fetal Biodistribution in the Nonhuman Primate","volume":"276","author":"Oh","year":"2015","journal-title":"Radiology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1001\/jama.2016.12126","article-title":"Association Between MRI Exposure During Pregnancy and Fetal and Childhood Outcomes","volume":"316","author":"Ray","year":"2016","journal-title":"JAMA"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Gatta, G., Di Grezia, G., Cuccurullo, V., Sardu, C., Iovino, F., Comune, R., Ruggiero, A., Chirico, M., La Forgia, D., and Fanizzi, A. (2021). MRI in Pregnancy and Precision Medicine: A Review from Literature. J. Pers. Med., 12.","DOI":"10.3390\/jpm12010009"},{"key":"ref_46","unstructured":"US FDA (2008). Requirement for Pregnancy and Lactation Labeling. Fed. Regist., 73, 104."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1097\/RLI.0000000000000681","article-title":"Human hair as a possible surrogate marker of retained tissue gadolinium: A pilot autopsy study correlating gadolinium concentrations in hair with brain and other tissues among decedents who received gadolinium-based contrast agents","volume":"55","author":"Hasegawa","year":"2020","journal-title":"Investig. Radiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1039\/c1mt00054c","article-title":"Simple and rapid quantification of gadolinium in urine and blood plasma samples by means of total reflection X-ray fluorescence (TXRF)","volume":"3","author":"Telgmann","year":"2011","journal-title":"Metallomics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/j.mri.2016.09.003","article-title":"Gadolinium deposition: Is it chelated or dissociated gadolinium? How can we tell?","volume":"34","author":"Tweedle","year":"2016","journal-title":"Magn. Reson. Imaging"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jaad.2009.12.044","article-title":"Quantification of gadolinium in fresh skin and serum samples from patients with nephrogenic systemic fibrosis","volume":"64","author":"Christensen","year":"2011","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4419","DOI":"10.1038\/s41598-018-22511-6","article-title":"Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents","volume":"8","author":"Rees","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1080\/15563650.2019.1681442","article-title":"Gadolinium-based contrast agents\u2013what is the evidence for \u2018gadolinium deposition disease\u2019and the use of chelation therapy?","volume":"58","author":"Layne","year":"2020","journal-title":"Clin. Toxicol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Bose, C., Megyesi, J.K., Shah, S.V., Hiatt, K.M., Hall, K.A., Karaduta, O., and Swaminathan, S. (2015). Evidence Suggesting a Role of Iron in a Mouse Model of Nephrogenic Systemic Fibrosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136563"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1093\/ndtplus\/sfp042","article-title":"Chelation of gadolinium with deferoxamine in a patient with nephrogenic systemic fibrosis","volume":"2","author":"Leung","year":"2009","journal-title":"Clin. Kidney J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/s41598-018-37348-2","article-title":"Removal of a gadolinium based contrast agent by a novel sorbent hemoperfusion in a chronic kidney disease (CKD) rodent model","volume":"9","author":"Ngamcherdtrakul","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_56","unstructured":"Aaseth, J., Crisponi, G., and Anderson, O. (2016). Chelation Therapy in the Treatment of Metal Intoxication, Academic Press."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/6\/742\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:17:49Z","timestamp":1760138269000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/12\/6\/742"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,24]]},"references-count":56,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["biom12060742"],"URL":"https:\/\/doi.org\/10.3390\/biom12060742","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,24]]}}}