title: Clinical Applications of Simultaneous PET/MR Imaging Using (R)-[11C]-Verapamil with Cyclosporin A: Preliminary Results on a Surrogate Marker of Drug-Resistant Epilepsy.
abstract: OBJECTIVE
  The development of resistance to antiepileptic drugs is explained well by the transporter hypothesis, which suggests that drug resistance is caused by inadequate penetration of drugs into the brain barrier as a result of increased levels of efflux transporter such as p-glycoprotein. To evaluate the brain expression of p-glycoprotein in patients with drug-resistant epilepsy, including neocortical epilepsy, we developed a noninvsive quantitative analysis including asymmetry indices based on (R)-[(11)C]-verapamil PET/MR imaging with cyclosporin A, a p-glycoprotein inhibitor.
  
  
  METHODS
  Six patients with drug-resistant epilepsy, 5 patients with drug-sensitive epilepsy, and 8 healthy controls underwent dynamic (R)-[(11)C]-verapamil PET/MR imaging with an intravenous infusion of cyclosporin A. Asymmetry indices [(Right Region - Left Region)/(Right Region + Left Region) × 200%] of the standard uptake values in each of the paired lobes were calculated.
  
  
  RESULTS
  All patients with drug-resistant epilepsy had significantly different asymmetry from the healthy controls, whereas all patients with drug-sensitive epilepsy had asymmetry similar to that in healthy controls. In the temporal lobe, the asymmetry indices of patients with left temporal lobe drug-resistant epilepsy were more positive than those of healthy controls (healthy controls: 4.0413 ± 1.7452; patients: 7.2184 ± 1.8237; P = .048), and those of patients with right temporal drug-resistant epilepsy were more negative (patients: -1.6496 ± 3.4136; P = .044). In addition, specific regions that had significant asymmetry were different between the lateral and medial temporal lobe epilepsy groups. In the frontal lobe, the asymmetry index of patients with right frontal lobe drug-resistant epilepsy was more negative than that in healthy controls.
  
  
  CONCLUSIONS
  We confirmed that statistical parametric mapping analysis by using asymmetry indices of (R)-[(11)C]-verapamil PET/MR imaging with cyclosporin A could be used as a surrogate marker for drug-resistant epilepsy, and this approach might be helpful for localizing or lateralizing the epileptic zone.
authors.affiliation: From the Department of Neurology (J.-W.S., K.C., K.-H.J., S.-T.L., J.M., D.Y.L., S.K.L.), Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute Department of Neurology (J.-W.S.), CHA Bundang Medical Center, CHA University, Seongnam, Korea.
authors.forename: J-W
authors.identifier: http://orcid.org/0000-0003-2155-9068
authors.initials: JW
authors.lastname: Shin
authors.affiliation: From the Department of Neurology (J.-W.S., K.C., K.-H.J., S.-T.L., J.M., D.Y.L., S.K.L.), Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute.
authors.forename: K
authors.identifier: http://orcid.org/0000-0001-5863-0302
authors.initials: K
authors.lastname: Chu
authors.affiliation: Department of Nuclear Medicine (S.A.S., Y.-S.L., J.S.L., D.S.L.) Department of Biomedical Sciences (S.A.S., J.S.L.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: S A
authors.identifier: http://orcid.org/0000-0002-0181-4749
authors.initials: SA
authors.lastname: Shin
authors.affiliation: From the Department of Neurology (J.-W.S., K.C., K.-H.J., S.-T.L., J.M., D.Y.L., S.K.L.), Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute.
authors.forename: K-H
authors.identifier: http://orcid.org/0000-0003-1433-8005
authors.initials: KH
authors.lastname: Jung
authors.affiliation: From the Department of Neurology (J.-W.S., K.C., K.-H.J., S.-T.L., J.M., D.Y.L., S.K.L.), Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute.
authors.forename: S-T
authors.identifier: http://orcid.org/0000-0003-4767-7564
authors.initials: ST
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine (S.A.S., Y.-S.L., J.S.L., D.S.L.) Department of Molecular Medicine and Biopharmaceutical Sciences (Y.-S.L., D.S.L.), Graduate School of Convergence Science and Technology, Kyunggi, South Korea.
authors.forename: Y-S
authors.identifier: http://orcid.org/0000-0003-1640-2090
authors.initials: YS
authors.lastname: Lee
authors.affiliation: From the Department of Neurology (J.-W.S., K.C., K.-H.J., S.-T.L., J.M., D.Y.L., S.K.L.), Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute.
authors.forename: J
authors.identifier: http://orcid.org/0000-0003-1282-4528
authors.initials: J
authors.lastname: Moon
authors.affiliation: From the Department of Neurology (J.-W.S., K.C., K.-H.J., S.-T.L., J.M., D.Y.L., S.K.L.), Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute.
authors.forename: D Y
authors.identifier: http://orcid.org/0000-0002-7379-5102
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine (S.A.S., Y.-S.L., J.S.L., D.S.L.) Department of Biomedical Sciences (S.A.S., J.S.L.), Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: J S
authors.identifier: http://orcid.org/0000-0001-7623-053X
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine (S.A.S., Y.-S.L., J.S.L., D.S.L.) Department of Molecular Medicine and Biopharmaceutical Sciences (Y.-S.L., D.S.L.), Graduate School of Convergence Science and Technology, Kyunggi, South Korea.
authors.forename: D S
authors.identifier: http://orcid.org/0000-0003-1627-6557
authors.initials: DS
authors.lastname: Lee
authors.affiliation: From the Department of Neurology (J.-W.S., K.C., K.-H.J., S.-T.L., J.M., D.Y.L., S.K.L.), Comprehensive Epilepsy Center, Laboratory for Neurotherapeutics, Biomedical Research Institute sangkun2923@gmail.com.
authors.forename: S K
authors.identifier: http://orcid.org/0000-0003-1908-0699
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D016572:Cyclosporine; D000069279:Drug Resistant Epilepsy / Q000000981:diagnostic imaging*; D004833:Epilepsy, Temporal Lobe / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods*; D049268:Positron-Emission Tomography / Q000379:methods; D014700:Verapamil
chemical_list: D015415:Biomarkers; D016572:Cyclosporine; D014700:Verapamil