RT Journal Article SR Electronic T1 18F-Flumazenil: A γ-Aminobutyric Acid A–Specific PET Radiotracer for the Localization of Drug-Resistant Temporal Lobe Epilepsy JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1270 OP 1277 DO 10.2967/jnumed.112.107359 VO 54 IS 8 A1 Lucy Vivash A1 Marie-Claude Gregoire A1 Eddie W. Lau A1 Robert E. Ware A1 David Binns A1 Peter Roselt A1 Viviane Bouilleret A1 Damian E. Myers A1 Mark J. Cook A1 Rodney J. Hicks A1 Terence J. O’Brien YR 2013 UL http://jnm.snmjournals.org/content/54/8/1270.abstract AB 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.