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Our main objective was to examine adult mice subjected to dietary iron deficiency (ID) for possible changes in the content of TfR1 in BCECs and the influence thereof on the uptake and possible transport across the blood\u2013brain barrier (BBB) of high\u2010affinity, rat anti\u2010mouse transferrin receptor IgG2a antibody (clone RI7217) targeting the TfR1. We subjected adult, female mice to dietary ID for 8\u2009weeks. Iron and copper were measured using inductively coupled plasma mass spectrometry (ICP\u2010MS) in various tissues, including total brain, and fractions of brain tissue separated to contain a capillary enriched fraction (\u201ccapillary fraction\u201d) and a post\u2010capillary, non\u2010endothelial\u2010containing brain parenchymal fraction (\u201cbrain fraction\u201d). Possible effects of ID on the cerebral angioarchitecture were estimated using 3D confocal microscopy of optically cleared brain samples labeled using intravenous injection of wheat germ agglutinin with subsequent machine learning\u2010based segmentation and vascular tracing. TfR1 was quantified using ELISA. RI7217 antibodies were conjugated with 1.4\u2009nm nanogold and brain uptake quantified using ICP\u2010MS. ID significantly reduced the iron content in the capillary fraction, liver, spleen, kidney, heart, and skeletal muscles. ID increased the copper content in the brain. Analysis of cerebral cortical angioarchitecture revealed no changes following dietary ID, except for a minor increase in tortuosity of small\u2010caliber vessels. Following ID, the concentration of TfR1 protein remained unchanged in total brain, and the isolated capillaries and brain fraction. In contrast, the uptake of nanogold\u2010conjugated RI7217 was increased in total brain, the brain fraction, liver, spleen, and isolated retinae. The targeting to TfR1 in ID hence suggested increased brain uptake of RI7217. Hypothetically, elevated transport of RI7217 could occur due to increased trafficking of TfR1\u2010containing vesicles through BCECs in ID.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70300-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70300","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T05:10:17Z","timestamp":1764220217000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dietary Iron Deficiency in Adult Mice Increases Brain Uptake of High\u2010Affinity, Anti\u2010Transferrin Receptor Antibody\n                    <scp>RI7217<\/scp>"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6731-2370","authenticated-orcid":false,"given":"Serhii","family":"Kostrikov","sequence":"first","affiliation":[{"name":"Department of Health Technology Technical University of Denmark  Kongens Lyngby Denmark"},{"name":"Centre for Auditory Neuroscience, Hearing Systems, Department of Health Technology Technical University of Denmark  Kongens Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasper Bendix","family":"Johnsen","sequence":"additional","affiliation":[{"name":"Department of Health Technology Technical University of Denmark  Kongens Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2086-4693","authenticated-orcid":false,"given":"Annette","family":"Burkhart","sequence":"additional","affiliation":[{"name":"Neurobiology Research and Drug Delivery, Department of Health Science and Technology Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steinunn Sara","family":"Helgud\u00f3ttir","sequence":"additional","affiliation":[{"name":"Neurobiology Research and Drug Delivery, Department of Health Science and Technology Aalborg University  Aalborg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Lars","family":"Andresen","sequence":"additional","affiliation":[{"name":"Department of Health Technology Technical University of Denmark  Kongens Lyngby 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