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

Abstract

Studies report that 11 C-flumazenil (FMZ) PET more specifically localizes the epileptogenic zone in patients with medically refractory focal epilepsy than 18 F-FDG PET. However, practical aspects of 11 C use limit clinical application. We report a phase I/IIa study assessing the clinical use of 18 F-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 18 F-FMZ PET and static interictal 18 F-FDG PET scans were compared in healthy controls (n 5 17 for 18 F-FMZ and n 5 20 for 18 F-FDG) and TLE patients with mesial temporal sclerosis on MR imaging (MTS, n 5 12) and with normal MR imaging (NL TLE, n 5 19). Masked visual assessment of images was undertaken. Parametric images of 18 F-FMZ binding potential (BP ND ) were generated using the simplified reference tissue model. Region-of-interest analysis on coregistered MR images and statistical parametric mapping were used to quantify 18 F-FMZ BP ND and 18 F-FDG uptake in the temporal lobe. Results: The visual assessment of static standardized uptake value images showed 18 F-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 18 F-FDG PET. However, the 18 F-FMZ standardized uptake value images were falsely localizing in 3 of 31 patients (10%). Region-of-interest analysis demonstrated reductions in ipsilateral hippocampal 18 F-FMZ BP ND in patients with either MTS or NL TLE, compared with controls subjects. Ipsilateral hippocampal 18 F-FMZ BP ND was independent of both hippocampal volume and 18 F-FDG uptake, whereas ipsilateral hippocampal volume was correlated with 18 F-FDG uptake (r 2 5 0.69, P , 0.0001). Statistical parametric mapping analysis demonstrated decreased uptake in 14 of 31 (45%) cases with 18 F-FMZ PET and 18 of 29 (62%) with 18 F-FDG PET. Cluster size was significantly smaller on 18 F-FMZ than 18 F-FDG images (37 vs. 160 voxels, P , 0.01). Conclusion: 18 F-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 18 F-FDG PET, with a more restricted region of abnormality.

Neuroimaging of epilepsy

“…FMZ PET was more sensitive than FDG-PET for detection of neocortical seizure onset in children with extratemporal-lobe epilepsy (Muzik et al, 2000). Similar results have been obtained with 18 F-flumazenil, which may be easier to use due to the longer ligand half-life (Vivash et al, 2013). Not all studies show consistent localizing value (Koepp et al, 2000).…”

Recent imaging advances in neurology

“…In particular, patients free of seizures after surgery had significantly different mesial temporal asymmetry for 5-HT 1A receptor densities as evaluated with [ 18 F]FCWAY and glucose metabolism measured with [ 18 F]FDG PET [116]. [ 11-C]Flumazenil PET provides evidence for a more restricted region of abnormality in patients with drug-resistant temporal lobe epilepsy and thus give localizing information which is complimentary to [ 18 F]FDG PET [117]. Overall, it seems that surgical approaches to intractable epilepsy could benefit from the use of PET, although more studies in conjunction with electroencephalographic mapping of epileptogenic areas are needed.…”

Nuclear Medicine Methods in Epilepsy

“…SPECT için kullanılan radyofarmasötikler Tc99m HMPAO ve Tc-99m ECD'dir. PET görüntüleme için en yaygın olarak kullanılan radyoaktif madde F-18 FDG olup F-18 flumazenil (FMZ) de nöbet alanını gösterir hatta FDG'ye göre daha sınırlı bir alanda lokalize olmaktadır (7). Bu bölümde özel olarak diğer bir radyofarmasötik ismi belirtilmediği sürece PET'den kasıt F-18 FDG PET olarak anlaşılmalıdır.…”

“…Hatta farklı bir radyofarmasötik madde olan F-18 FCWAY isimli ajan ile yapılan PET çalışmaları bu ajanın MR negatif grupta FDG'den daha faydalı olabileceğini göstermektedir (12). Temporal lob epilepsisi olan hastalarda en sık saptanan yapısal anomali hipokampal skleroz olup bu bulgu aynı zamanda iyi cerrahi sonucun da en güvenilir göstergesidir (7,13). Van Paesschen ve ark.…”