title: 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 = 17 for (18)F-FMZ and n = 20 for (18)F-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 (18)F-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 (18)F-FMZ BPND 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 BPND in patients with either MTS or NL TLE, compared with controls subjects. Ipsilateral hippocampal (18)F-FMZ BPND was independent of both hippocampal volume and (18)F-FDG uptake, whereas ipsilateral hippocampal volume was correlated with (18)F-FDG uptake (r(2) = 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).
  
  
  CONCLUSIONS
  (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.
authors.affiliation: Departments of Medicine and Neurology, Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Royal Parade, Parkville, Victoria, Australia.
authors.forename: Lucy
authors.initials: L
authors.lastname: Vivash
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gregoire
authors.forename: Eddie W
authors.initials: EW
authors.lastname: Lau
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ware
authors.forename: David
authors.initials: D
authors.lastname: Binns
authors.forename: Peter
authors.initials: P
authors.lastname: Roselt
authors.forename: Viviane
authors.initials: V
authors.lastname: Bouilleret
authors.forename: Damian E
authors.initials: DE
authors.lastname: Myers
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cook
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.forename: Terence J
authors.initials: TJ
authors.lastname: O'Brien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000613:Aminobutyrates / Q000378:metabolism*; D016022:Case-Control Studies; D004351:Drug Resistance; D004833:Epilepsy, Temporal Lobe / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005442:Flumazenil / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000009:adverse effects / Q000379:methods*; D011849:Radioactive Tracers; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C483765:2'-fluoroflumazenil; D000613:Aminobutyrates; D011849:Radioactive Tracers; D005442:Flumazenil; C012223:alpha-aminobutyric acid
keywords: 18F-flumazenil; FDG; fluorodeoxyglucose; positron emission tomography; temporal lobe epilepsy