{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:56:13Z","timestamp":1791035773724,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T00:00:00Z","timestamp":1744243200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Permeability\u2010glycoprotein (P\u2010gp), a crucial efflux pump transporter encoded by the ABCB1 gene, plays a pivotal role in drug disposition at the blood\u2013brain barrier (BBB) and is involved in the pharmacokinetics of numerous therapeutic agents. This study investigates differences in P\u2010gp function at the BBB between males and females in a cohort of older (55+) healthy volunteers (HV) using [\n                    <jats:sup>18<\/jats:sup>\n                    F]MC225 and PET. Twenty HV (11 males and 9 females), free from medications that affect P\u2010gp function and without a history of neurological or psychiatric disorders, underwent [\n                    <jats:sup>18<\/jats:sup>\n                    F]MC225 PET scans with manual arterial blood sampling. Tissue time\u2010activity curves (TAC) were extracted using the Hammers maximum\u2010probability atlas. Whole\u2010blood TAC was derived from the internal carotid arteries, calibrated using manual arterial samples, and adjusted for the plasma\u2010to\u2010whole blood ratio and plasma parent fraction to obtain the image\u2010derived input function. The volume of distribution (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    ) was estimated using a reversible two\u2010tissue compartment model, yielding the parameter of interest. Statistical analysis revealed no significant differences in P\u2010gp function between sexes, based on\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>T<\/jats:sub>\n                    values across various brain regions (Cohen's\n                    <jats:italic>d<\/jats:italic>\n                    \u2009&lt;\u20090.2). Furthermore, the arterial blood concentration, plasma parent fraction, and microparameters demonstrated no statistical differences between male and female participants. These findings suggest that P\u2010gp function at the BBB does not exhibit substantial sex\u2010related variability in healthy older adults (55+). For future [\n                    <jats:sup>18<\/jats:sup>\n                    F]MC225 PET studies, a mixed\u2010sex population can serve as an appropriate age\u2010matched control group for neurodegenerative studies. Further research is needed to explore sex\u2010related differences in younger populations, particularly with respect to hormonal cycles.\n                  <\/jats:p>","DOI":"10.1111\/cts.70196","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T07:39:21Z","timestamp":1744270761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Exploratory Study of Sex Differences in P\u2010Glycoprotein Function at the Blood\u2013Brain Barrier"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2243-3141","authenticated-orcid":false,"given":"Giordana","family":"Salvi de Souza","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"School of Medicine, PUCRS  Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7159-5759","authenticated-orcid":false,"given":"Wanling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1526-6923","authenticated-orcid":false,"given":"Pascalle","family":"Mossel","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"Department of Radiology Leiden University Medical Center  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0761-9002","authenticated-orcid":false,"given":"Joost F.","family":"Somsen","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9293-1402","authenticated-orcid":false,"given":"Anna L.","family":"Bartels","sequence":"additional","affiliation":[{"name":"Department of Neurology Ommelander Ziekenhuis Groningen  Scheemda the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1609-7727","authenticated-orcid":false,"given":"Cristiane R. G.","family":"Furini","sequence":"additional","affiliation":[{"name":"School of Medicine, PUCRS  Porto Alegre Brazil"},{"name":"Laboratory of Cognition and Memory Neurobiology, Brain Institute, PUCRS  Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1237-2891","authenticated-orcid":false,"given":"Adriaan A.","family":"Lammertsma","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4971-2477","authenticated-orcid":false,"given":"Charalampos","family":"Tsoumpas","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8599-8129","authenticated-orcid":false,"given":"Gert","family":"Luurtsema","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2022.e09777"},{"issue":"8","key":"e_1_2_9_3_1","first-page":"1583","article-title":"Disrupting P\u2010Glycoprotein Function in Clinical Settings: What Can We Learn From the Fundamental Aspects of This Transporter?","volume":"6","author":"Chung F. 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