F-18-Flumazenil: A gamma-Aminobutyric Acid A-Specific PET Radiotracer for the Localization of Drug-Resistant Temporal Lobe Epilepsy

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

来源：Journal of Nuclear Medicine, 2013, 54(8): 1270-1277.

DOI：10.2967/jnumed.112.107359

• F-18-flumazenil
• positron emission tomography
• FDG
• temporal lobe epilepsy
• fluorodeoxyglucose

Studies report that C-11-flumazenil (FMZ) PET more specifically localizes the epileptogenic zone in patients with medically refractory focal epilepsy than F-18-FDG PET. However, practical aspects of C-11 use limit clinical application. We report a phase I/IIa study assessing the clinical use of F-18-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 F-18-FMZ PET and static interictal F-18-FDG PET scans were compared in healthy controls (n = 17 for F-18-FMZ and n = 20 for F-18-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 F-18-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 F-18-FMZ BPND and F-18-FDG uptake in the temporal lobe. Results: The visual assessment of static standardized uptake value images showed F-18-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 F-18-FDG PET. However, the F-18-FMZ standardized uptake value images were falsely localizing in 3 of 31 patients (10%). Region-of-interest analysis demonstrated reductions in ipsilateral hippocampal F-18-FMZ BPND in patients with either MTS or NL TLE, compared with controls subjects. Ipsilateral hippocampal F-18-FMZ BPND was independent of both hippocampal volume and F-18-FDG uptake, whereas ipsilateral hippocampal volume was correlated with F-18-FDG uptake (r(2) = 0.69, P < 0.0001). Statistical parametric mapping analysis demonstrated decreased uptake in 14 of 31 (45%) cases with F-18-FMZ PET and 18 of 29 (62%) with F-18-FDG PET. Cluster size was significantly smaller on F-18-FMZ than F-18-FDG images (37 vs. 160 voxels, P < 0.01). Conclusion: F-18-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 F-18-FDG PET, with a more restricted region of abnormality.

• 出版日期2013-8