18F-flumazenil: A g-aminobutyric acid A-specific PET radiotracer for the localization of drug-resistant temporal lobe epilepsy

Lucy Vivash, Marie Claude Gregoire, Eddie W. Lau, Robert E. Ware, David Binns, Peter Roselt, Viviane Bouilleret, Damian E. Myers, Mark J. Cook, Rodney J. Hicks, Terence J. O'Brien

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Studies report that 11C-flumazenil (FMZ) PET more specifically localizes the epileptogenic zone in patients with medically refractory focal epilepsy than 18F-FDG PET. However, practical aspects of 11C use limit clinical application. We report a phase I/IIa study assessing the clinical use of 18F-FMZ PET for the localization of the epileptogenic zone in patients with drug-resistant temporal lobe epilepsy (TLE). Receptor binding was quantified using kinetic modeling that did not require arterial sampling. Methods: Dynamic 18F-FMZ PET and static interictal 18F-FDG PET scans were compared in healthy controls (n = 17 for 18F-FMZ and n = 20 for 18F-FDG) and TLE patients with mesial temporal sclerosis on MR imaging (MTS, n = 12) and with normal MR imaging (NL TLE, n = 19). Masked visual assessment of images was undertaken. Parametric images of 18FFMZ binding potential (BPND) were generated using the simplified reference tissue model. Region-of-interest analysis on coregistered MR images and statistical parametric mapping were used to quantify 18F-FMZ BPND and 18F-FDG uptake in the temporal lobe. Results: The visual assessment of static standardized uptake value images showed 18F-FMZ PET to have high specificity (16/17 [94%]) and moderate sensitivity (21/31 [68%]) for the localization of the epileptogenic zone, with a more restricted abnormality than 18FFDG PET. However, the 18F-FMZ standardized uptake value images were falsely localizing in 3 of 31 patients (10%). Region-of-interest analysis demonstrated reductions in ipsilateral hippocampal 18FFMZ BP ND in patients with either MTS or NL TLE, compared with controls subjects. Ipsilateral hippocampal 18F-FMZ BPND was independent of both hippocampal volume and 18F-FDG uptake, whereas ipsilateral hippocampal volume was correlated with 18F-FDG uptake (r2 = 0.69, P < 0.0001). Statistical parametric mapping analysis demonstrated decreased uptake in 14 of 31 (45%) cases with 18F-FMZ PET and 18 of 29 (62%) with 18F-FDG PET. Cluster size was significantly smaller on 18F-FMZ than 18F-FDG images (37 vs. 160 voxels, P < 0.01). Conclusion: 18F-FMZ PET has potential as a clinical tool for the localization of the epileptogenic zone in the presurgical evaluation of drug-resistant TLE, providing information complementary to 18F-FDG PET, with a more restricted region of abnormality. COPYRIGHT

Original languageEnglish
Pages (from-to)1270-1277
Number of pages8
JournalJournal of Nuclear Medicine
Issue number8
Publication statusPublished - 1 Aug 2013
Externally publishedYes


  • F-flumazenil
  • FDG
  • Fluorodeoxyglucose
  • Positron emission tomography
  • Temporal lobe epilepsy

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