{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:47:08Z","timestamp":1784130428708,"version":"3.55.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1099","license":[{"start":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T00:00:00Z","timestamp":1559692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>To investigate the role of transporter proteins in gadolinium (Gd) distribution and retention in the brain after one high-dose injection of Gd-based contrast agent (GBCA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and materials:<\/jats:title>\n                  <jats:p>30 ddY mice were randomly divided into three treatment groups to be intravenously injected with either Gadodiamide (linear GBCA), Gadobutrol (macrocyclic GBCA), or Gadoterate (macrocyclic GBCA) at a dose of 5\u2009mmol\/kg, while five mice in the control group received 250\u2009\u00b5L saline. Five minutes (5\u2009min) and ten days (10d) post-injection, the cerebrospinal fluid (CSF), choroid plexus (CP), and meninges and associated vasculature (MAV) were collected. The brain was then dissected to obtain the olfactory bulb, cerebral cortex, hippocampus, cerebellum, and brainstem. Proteins were extracted and separated by a size-exclusion high-performance liquid chromatography (SEC) system, and Gd concentrations were quantified by inductively coupled plasma mass spectrometry (ICP-MS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>5 m post-injection, the Gadodiamide group had the highest Gd concentration, while Gadoterate had the lowest Gd concentration in all parts of the brain (p &amp;lt; .05). Gd concentration was highest in the cerebrospinal fluid (CSF) of the Gadodiamide group (578.4 \u00b1 135.3\u2009nmol), while Gd concentration was highest in MAV in the Gadobutrol group (379.7 \u00b1 75.4\u2009nmol) at 5\u2009min post-injection. At 10d, in spite of the significant decrease of Gd from all GBCAs ( p &amp;lt; 0.01), retained Gd from Gadodiamide was detected all over the brain in several molecules that varied in size. Gd from Gadobutrol detected in the olfactory bulb (8.7 \u00b1 4.5\u2009nmol) was significantly higher than in other parts of the brain. Although most Gd from Gadobutrol was found in molecules similar in size to Gadobutrol, it was also found in several protein molecules of molecular size larger than the contrast agents. Only a small amount of Gd from Gadoterate was found in the brain.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion:<\/jats:title>\n                  <jats:p>GBCAs may be able to pass through intact brain barriers, and the chemical structures of GBCAs may affect the penetration capability of Gd into the brain. Retained Gd in the brain tissue from Gadodiamide and Gadobutrol may be bound to some organic molecules, including proteins.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Advances in knowledge:<\/jats:title>\n                  <jats:p>Intact GBCA are able to penetrate a series of brain barrier immediately after administration regardless the type of the chelate. Gd may be bound with macromolecules that may cause Gd retention in the brain.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1259\/bjr.20190062","type":"journal-article","created":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T16:05:29Z","timestamp":1556813129000},"source":"Crossref","is-referenced-by-count":12,"title":["Quantitative analysis of Gd in the protein content of the brain following single injection of gadolinium-based contrast agents (GBCAs) by size exclusion chromatography"],"prefix":"10.1093","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8165-6893","authenticated-orcid":false,"given":"Achmad Adhipatria Perayabangsa","family":"Kartamihardja","sequence":"first","affiliation":[{"name":"Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Hanaoka","sequence":"additional","affiliation":[{"name":"Department of Bioimaging and Information Analysis, Gunma University Graduate School of Medicine , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Putri","family":"Andriana","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satomi","family":"Kameo","sequence":"additional","affiliation":[{"name":"Department of Public Health, Gunma University Graduate School of Medicine , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Koyama","sequence":"additional","affiliation":[{"name":"Department of Public Health, Gunma University Graduate School of Medicine , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshito","family":"Tsushima","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,5]]},"reference":[{"key":"2024050214515455400_b1","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":"2024050214515455400_b2","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1097\/RLI.0000000000000072","article-title":"Progressive increase of T1 signal intensity of the 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