{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:10:29Z","timestamp":1791475829329,"version":"4.3.4"},"reference-count":44,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>[18F]MC225 has been developed as a weak substrate of P-glycoprotein (P-gp) aimed to measure changes in the P-gp function at the blood\u2013brain barrier with positron emission tomography. This study evaluates [18F]MC225 kinetics in non-human primates and investigates the effect of both scan duration and P-gp inhibition. Three rhesus monkeys underwent two 91-min dynamic scans with blood sampling at baseline and after P-gp inhibition (8 mg\/kg tariquidar). Data were analyzed using the 1-tissue compartment model (1-TCM) and 2-tissue compartment model (2-TCM) fits using metabolite-corrected plasma as the input function and for various scan durations (10, 20, 30, 60, and 91 min). The preferred model was chosen according to the Akaike information criterion and the standard errors (%) of the estimated parameters. For the 91-min scan duration, the influx constant K1 increased by 40.7% and the volume of distribution (VT) by 30.4% after P-gp inhibition, while the efflux constant k2 did not change significantly. Similar changes were found for all evaluated scan durations. K1 did not depend on scan duration (10 min\u2500K1 = 0.2191 vs 91 min\u2500K1 = 0.2258), while VT and k2 did. A scan duration of 10 min seems sufficient to properly evaluate the P-gp function using K1 obtained with 1-TCM. For the 91-min scan, VT and K1 can be estimated with a 2-TCM, and both parameters can be used to assess P-gp function.<\/jats:p>","DOI":"10.1021\/acs.molpharmaceut.0c00514","type":"journal-article","created":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T12:58:59Z","timestamp":1596632339000},"page":"3477-3486","source":"Crossref","is-referenced-by-count":21,"title":["Pharmacokinetic Modeling of [18F]MC225\nfor Quantification of the P-Glycoprotein Function at the Blood\u2013Brain\nBarrier in Non-Human Primates with PET"],"prefix":"10.1021","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9803-4708","authenticated-orcid":true,"given":"Lara","family":"Garci\u0301a-Varela","sequence":"first","affiliation":[{"name":"University of Groningen, University Medical Center Groningen , , Hanzeplein 1 , P.O. Box 30001, ,","place":["Groningen, the Netherlands, 9713 GZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wejdan M.","family":"Arif","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen , , Hanzeplein 1 , P.O. Box 30001, ,","place":["Groningen, the Netherlands, 9713 GZ"]},{"name":"College of Applied Medical Sciences, King Saud University , , ,","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Va\u0301llez Garci\u0301a","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen , , Hanzeplein 1 , P.O. Box 30001, ,","place":["Groningen, the Netherlands, 9713 GZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeharu","family":"Kakiuchi","sequence":"additional","affiliation":[{"name":"Hamamatsu Photonics KK , , 5000 Hirakuchi , Hamakita, , ,","place":["Hamamatsu, Shizuoka, Japan, 434-8601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Ohba","sequence":"additional","affiliation":[{"name":"Hamamatsu Photonics KK , , 5000 Hirakuchi , Hamakita, , ,","place":["Hamamatsu, Shizuoka, Japan, 434-8601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiro","family":"Harada","sequence":"additional","affiliation":[{"name":"Hamamatsu Photonics KK , , 5000 Hirakuchi , Hamakita, , ,","place":["Hamamatsu, Shizuoka, Japan, 434-8601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Tago","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Institute of Gerontology , , 35-2 Sakae-cho , Itabashi-ku, ,","place":["Tokyo, Japan, 173-0015"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip H.","family":"Elsinga","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen , , Hanzeplein 1 , P.O. Box 30001, ,","place":["Groningen, the Netherlands, 9713 GZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Tsukada","sequence":"additional","affiliation":[{"name":"Hamamatsu Photonics KK , , 5000 Hirakuchi , Hamakita, , ,","place":["Hamamatsu, Shizuoka, Japan, 434-8601"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-7746","authenticated-orcid":true,"given":"Nicola Antonio","family":"Colabufo","sequence":"additional","affiliation":[{"name":"University of Bari Aldo Moro , , ,","place":["Bari, Italy, 70121"]},{"name":"Biofordrug, Spin-off Universita\u0300 degli Studi di Bari \u201cA. Moro\u201d , via Dante 99 , Triggiano, ,","place":["Bari, Italy, 70019"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi A. J. O.","family":"Dierckx","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen , , Hanzeplein 1 , P.O. Box 30001, ,","place":["Groningen, the Netherlands, 9713 GZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aren","family":"van Waarde","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen , , Hanzeplein 1 , P.O. Box 30001, ,","place":["Groningen, the Netherlands, 9713 GZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Toyohara","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Institute of Gerontology , , 35-2 Sakae-cho , Itabashi-ku, ,","place":["Tokyo, Japan, 173-0015"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Boellaard","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen , , Hanzeplein 1 , P.O. Box 30001, ,","place":["Groningen, the Netherlands, 9713 GZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gert","family":"Luurtsema","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen , , Hanzeplein 1 , P.O. Box 30001, ,","place":["Groningen, the Netherlands, 9713 GZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,8,5]]},"reference":[{"key":"2026090110010430600_cit1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.pneurobio.2005.04.006","article-title":"Role of Drug Efflux\nTransporters in the Brain for Drug\nDisposition and Treatment of Brain Diseases","volume":"76","author":"Lo\u0308scher","year":"2005","journal-title":"Prog. 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Pharmacol.\nExp. Ther."},{"key":"2026090110010430600_cit26","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1038\/jcbfm.2015.19","article-title":"Approaching\nComplete Inhibition of P-Glycoprotein at\nthe Human Blood-Brain Barrier: An (R)-[11C]Verapamil PET Study","volume":"35","author":"Bauer","year":"2015","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"2026090110010430600_cit27","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/jcbfm.2009.265","article-title":"Assessment of Regional Differences in Tariquidar-Induced\nP-Glycoprotein Modulation at the Human Blood-Brain Barrier","volume":"30","author":"Bauer","year":"2010","journal-title":"J. Cereb. 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Ther."},{"key":"2026090110010430600_cit41","first-page":"127","article-title":"Tracer Kinetic\nModeling in PET","volume-title":"Positron Emission Tomography","author":"Carson","year":"2003"},{"key":"2026090110010430600_cit42","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.2967\/jnumed.118.210104","article-title":"P-Glycoprotein (ABCB1)\nInhibits the Influx and Increases\nthe Efflux of 11 C-Metoclopramide across the Blood-Brain Barrier:\nA PET Study on Non-Human Primates","volume":"118","author":"Auvity","year":"2018","journal-title":"J. Nucl.\nMed."},{"key":"2026090110010430600_cit43","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1021\/acschemneuro.9b00682","article-title":"Test-Retest Repeatability of [18F]MC225-PET in Rodents: A Tracer\nfor Imaging of P-gp Function","volume":"11","author":"Garci\u0301a-Varela","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"2026090110010430600_cit44","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s13550-020-00674-6","article-title":"Automated\nSynthesis, Preclinical Toxicity, and Radiation Dosimetry of [18F]MC225\nfor Clinical Use: A Tracer for Measuring P-Glycoprotein Function at\nthe Blood-Brain Barrier","volume":"10","author":"Toyohara","year":"2020","journal-title":"EJNMMI Res."}],"container-title":["Molecular Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.molpharmaceut.0c00514","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article-pdf\/17\/9\/3477\/67453480\/acs.molpharmaceut.0c00514.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article-pdf\/17\/9\/3477\/67453480\/acs.molpharmaceut.0c00514.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:01:10Z","timestamp":1788271270000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/mpohbp\/article\/17\/9\/3477\/507960\/Pharmacokinetic-Modeling-of-18F-MC225-for"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,5]]},"references-count":44,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,8,5]]},"published-print":{"date-parts":[[2020,9,8]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.molpharmaceut.0c00514","relation":{},"ISSN":["1543-8384","1543-8392"],"issn-type":[{"value":"1543-8384","type":"print"},{"value":"1543-8392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,5]]}}}