Ilyas-Feldmann, M;
Asselin, M-C;
Wang, S;
McMahon, A;
Anton-Rodriguez, J;
Brown, G;
Hinz, R;
... Koepp, M; + view all
(2020)
P-glycoprotein overactivity in epileptogenic developmental lesions measured in vivo using (R)-[¹¹C]verapamil PET.
Epilepsia
10.1111/epi.16581.
(In press).
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Abstract
OBJECTIVE: Overexpression of the drug transporter P-glycoprotein (P-gp) is thought to be involved in drug-resistance in epilepsy by extrusion of antiepileptic drugs (AEDs). We used positron emission tomography (PET) and the P-gp substrate radiotracer (R)-[11 C]verapamil (VPM) together with the third-generation P-gp inhibitor tariquidar (TQD) to evaluate P-gp function in individuals with drug-resistant epileptogenic developmental lesions. METHODS: Twelve healthy controls (7 male, median age 45, range 35-55 years), and two patients with epileptogenic developmental lesions (2 male, aged 24 and 62 years) underwent VPM-PET scans before and 60 minutes after a 30-minute infusion of 2 and 3 mg/kg TQD. The influx rate constant, VPM-K1 , was estimated from the first 10 minutes of dynamic data using a single-tissue compartment model with a VPM plasma input function. Statistical parametric mapping (SPM) analysis was used to compare individual patients with the healthy controls. RESULTS: At baseline, SPM voxel-based analysis revealed significantly lower uptake of VPM corresponding to the area of the epileptogenic developmental lesion compared to 12 healthy controls (P < .048). This was accentuated following P-gp inhibition with TQD. After TQD, the uptake of VPM was significantly lower in the area of the epileptogenic developmental lesion compared to controls (P < .002). SIGNIFICANCE: This study provides further evidence of P-gp overactivity in patients with drug-resistant epilepsy, irrespective of the type of lesion. Identifying P-gp overactivity as an underlying contributor to drug-resistance in individual patients will enable novel treatment strategies aimed at overcoming or reversing P-gp overactivity.
| Type: | Article |
|---|---|
| Title: | P-glycoprotein overactivity in epileptogenic developmental lesions measured in vivo using (R)-[¹¹C]verapamil PET |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/epi.16581 |
| Publisher version: | https://doi.org/10.1111/epi.16581 |
| Language: | English |
| Additional information: | Copyright © 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
| Keywords: | P-glycoprotein, drug-resistant epilepsy, positron emission tomography, tariquidar |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Experimental Epilepsy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10105393 |
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