{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:47:04Z","timestamp":1784130424796,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Magnetic Resonance Imaging"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Studies of gadolinium (Gd) clearance from animals in the first weeks after administration of gadolinium\u2010based contrast agents (GBCAs) have previously looked at solitary timepoints only. However, this does not give information on differences between GBCAs and between organs in terms of Gd elimination kinetics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To compare Gd levels in rat cerebellum, cerebrum, skin, and blood at 1, 2, 3, and 5\u2009weeks after repeated administration of macrocyclic GBCAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Type<\/jats:title><jats:p>Prospective.<\/jats:p><\/jats:sec><jats:sec><jats:title>Animal Model<\/jats:title><jats:p>One hundred eighty male Sprague\u2013Dawley rats randomized to three groups (<jats:italic>n<\/jats:italic>\u00a0=\u00a060\/group), received intravenous administrations of gadoteridol, gadoterate meglumine, or gadobutrol (0.6\u2009mmol\/kg for each) four times\/week for 5 consecutive weeks. Rats were sacrificed after washout periods of 1, 2, 3, or 5\u2009weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Field Strength\/Sequence<\/jats:title><jats:p>Not applicable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Assessment<\/jats:title><jats:p>Cerebellum, cerebrum, skin, and blood were harvested for Gd determination by inductively coupled plasma\u2010mass spectrometry (15 animals\/group\/all timepoints).<\/jats:p><\/jats:sec><jats:sec><jats:title>Statistical Tests<\/jats:title><jats:p>Anova and Dunnett's test (data with homogeneous variances and normal distribution). Kruskal\u2013Wallis and Wilcoxon's rank sum tests (data showing nonhomogeneous variances or a non\u2010normal distribution, significance levels: <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01, and <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gd levels in cerebellum, cerebrum, and skin were significantly lower after gadoteridol than after gadoterate and gadobutrol at all timepoints. Mean cerebellum Gd concentrations after gadoteridol, gadoterate, and gadobutrol decreased from 0.693, 0.878, and 1.011\u2009nmol Gd\/g at 1\u2009week to 0.144, 0.282, and 0.297\u2009nmol Gd\/g at 5\u2009weeks after injection. Similar findings were noted for cerebrum and skin. Conversely, significantly higher Gd levels were noted in blood after gadoteridol compared to gadobutrol at 1, 2, and 3\u2009weeks and compared to gadoterate at all timepoints.<\/jats:p><\/jats:sec><jats:sec><jats:title>Data Conclusion<\/jats:title><jats:p>Gadoteridol is eliminated more rapidly from rat cerebellum, cerebrum, and skin compared to gadoterate and gadobutrol in the first 5\u2009weeks after administration, resulting in lower levels of retained Gd in these tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Evidence Level<\/jats:title><jats:p>1<\/jats:p><\/jats:sec><jats:sec><jats:title>Technical Efficacy<\/jats:title><jats:p>Stage 5<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmri.27693","type":"journal-article","created":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T10:03:59Z","timestamp":1620727439000},"page":"1636-1644","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Gadolinium Clearance in the First 5\u2009Weeks After Repeated Intravenous Administration of Gadoteridol, Gadoterate Meglumine, and Gadobutrol to rats"],"prefix":"10.1002","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6619-0404","authenticated-orcid":false,"given":"Simona","family":"Bussi","sequence":"first","affiliation":[{"name":"Bracco Imaging SpA, Bracco Research Centre  Colleretto Giacosa TO Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Coppo","sequence":"additional","affiliation":[{"name":"Bracco Imaging SpA, Bracco Research Centre  Colleretto Giacosa TO Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bonaf\u00e8","sequence":"additional","affiliation":[{"name":"Bracco Imaging SpA, Bracco Research Centre  Colleretto Giacosa TO Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Rossi","sequence":"additional","affiliation":[{"name":"Bracco Imaging SpA, Bracco Research Centre  Colleretto Giacosa TO Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Colombo Serra","sequence":"additional","affiliation":[{"name":"Bracco Imaging SpA, Bracco Research Centre  Colleretto Giacosa TO Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Penard","sequence":"additional","affiliation":[{"name":"Charles River Saint Germain\u2010Nuelles  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5803-7867","authenticated-orcid":false,"given":"Miles A.","family":"Kirchin","sequence":"additional","affiliation":[{"name":"Bracco Imaging SpA, Global Medical &amp; Regulatory Affairs  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8852-4391","authenticated-orcid":false,"given":"Federico","family":"Maisano","sequence":"additional","affiliation":[{"name":"Bracco Imaging SpA, Bracco Research Centre  Colleretto Giacosa TO Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Tedoldi","sequence":"additional","affiliation":[{"name":"Bracco Imaging SpA, Bracco Research Centre  Colleretto Giacosa TO Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2020202903"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.13131669"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLI.0000000000000252"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLI.0000000000000344"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLI.0000000000000241"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLI.0000000000000352"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20160509"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLI.0000000000000575"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2017162857"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLI.0000000000000423"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2017161594"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.25822"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13244-019-0824-5"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2018180135"},{"key":"e_1_2_7_16_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). 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