{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:23:49Z","timestamp":1790645029244,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T00:00:00Z","timestamp":1593993600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Overexpression of the drug transporter P\u2010glycoprotein (P\u2010gp) is thought to be involved in drug\u2010resistance in epilepsy by extrusion of antiepileptic drugs (AEDs). We used positron emission tomography (PET) and the P\u2010gp substrate radiotracer (R)\u2010[<jats:sup>11<\/jats:sup>C]verapamil (VPM) together with the third\u2010generation P\u2010gp inhibitor tariquidar (TQD) to evaluate P\u2010gp function in individuals with drug\u2010resistant epileptogenic developmental lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twelve healthy controls (7 male, median age 45, range 35\u201055\u00a0years), and two patients with epileptogenic developmental lesions (2 male, aged 24 and 62\u00a0years) underwent VPM\u2010PET scans before and 60\u00a0minutes after a 30\u2010minute infusion of 2 and 3\u00a0mg\/kg TQD. The influx rate constant, VPM\u2010K<jats:sub>1<\/jats:sub>, was estimated from the first 10\u00a0minutes of dynamic data using a single\u2010tissue compartment model with a VPM plasma input function. Statistical parametric mapping (SPM) analysis was used to compare individual patients with the healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At baseline, SPM voxel\u2010based analysis revealed significantly lower uptake of VPM corresponding to the area of the epileptogenic developmental lesion compared to 12 healthy controls (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.048). This was accentuated following P\u2010gp inhibition with TQD. After TQD, the uptake of VPM was significantly lower in the area of the epileptogenic developmental lesion compared to controls (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study provides further evidence of P\u2010gp overactivity in patients with drug\u2010resistant epilepsy, irrespective of the type of lesion. Identifying P\u2010gp overactivity as an underlying contributor to drug\u2010resistance in individual patients will enable novel treatment strategies aimed at overcoming or reversing P\u2010gp overactivity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16581","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T10:45:16Z","timestamp":1594032316000},"page":"1472-1480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["P\u2010glycoprotein overactivity in epileptogenic developmental lesions measured in vivo using (R)\u2010[<sup>11<\/sup>C]verapamil PET"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2322-6534","authenticated-orcid":false,"given":"Maria","family":"Ilyas\u2010Feldmann","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy University College London Queen Square Institute of Neurology London UK"},{"name":"Chalfont Centre for Epilepsy Bucks UK"},{"name":"Wolfson Molecular Imaging Centre University of Manchester Manchester UK"},{"name":"Department of Neurology Epilepsy\u2010Center Berlin\u2010Brandenburg Charit\u00e9 \u2010 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Claude","family":"Asselin","sequence":"additional","affiliation":[{"name":"Wolfson Molecular Imaging Centre University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaonan","family":"Wang","sequence":"additional","affiliation":[{"name":"Wolfson Molecular Imaging Centre University of Manchester Manchester UK"},{"name":"Global Pharmacometrics Boehringer Ingelheim Ingelheim am Rhein Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"McMahon","sequence":"additional","affiliation":[{"name":"Wolfson Molecular Imaging Centre University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Anton\u2010Rodriguez","sequence":"additional","affiliation":[{"name":"Wolfson Molecular Imaging Centre University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Brown","sequence":"additional","affiliation":[{"name":"Wolfson Molecular Imaging Centre University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7808-9207","authenticated-orcid":false,"given":"Rainer","family":"Hinz","sequence":"additional","affiliation":[{"name":"Wolfson Molecular Imaging Centre University of Manchester Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1373-0681","authenticated-orcid":false,"given":"John S.","family":"Duncan","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy University College London Queen Square Institute of Neurology London UK"},{"name":"Chalfont Centre for Epilepsy Bucks UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1511-5893","authenticated-orcid":false,"given":"Sanjay M.","family":"Sisodiya","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy University College London Queen Square Institute of Neurology London UK"},{"name":"Chalfont Centre for Epilepsy Bucks UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Koepp","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Epilepsy University College London Queen Square Institute of Neurology London UK"},{"name":"Chalfont Centre for Epilepsy Bucks UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200002033420503"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1995.tb01657.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws147"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.121178"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2003.42802.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2004.06.005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh437"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl133"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2007.03.011"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.2005.00699.x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70109-1"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600349"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.108.059162"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1109\/NSSMIC.2010.5874334"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1109\/42.232247"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.460020402"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2000\/421719"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/118.4.1039"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01116.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000858"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802610792928095"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6616-10.2011"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)03573-X"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-007-0453-z"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00992-2"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A4566"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fepi.16581","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16581","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.16581","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16581","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T09:48:21Z","timestamp":1693907301000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.16581"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7]]},"references-count":26,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["10.1111\/epi.16581"],"URL":"https:\/\/doi.org\/10.1111\/epi.16581","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7]]},"assertion":[{"value":"2019-11-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}