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Title: [18F]-Flumazenil: A γ-aminobutyric acid A–specific PET radiotracer for the localisation of drug resistant temporal lobe epilepsy.
Authors: Vivash, L
Gregoire, M-C
Lau, E
Ware, R E
Binns, D
Roselt, P
Bouilleret, V
Myers, D E
Cook, M J
Hicks, R J
O’Brien, T J
Issue Date: 15-Jul-2013
Publisher: Soc Nuclear Medicine Inc
Citation: Vivash, L., Gregoire, M-C., Lau, E. W., Ware, R. E., Binns, D., Roselt, P., Bouilleret, V., Myers, D. E., Cook, M. J., Hicks, R. J., O’Brien, T. J. [18F]-Flumazenil: A GABAA-specific PET radiotracer for the localisation of drug resistant temporal lobe epilepsy. Journal of Nuclear Medicine, 54(8), 1-8 (2013).
Abstract: 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 18F-FMZ 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 18F-FDG 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 18F-FMZ BPND 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. © 2013 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
ISSN: 0161-5505
Appears in Collections:Journal Articles

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