Epilepsy imaging: Move over C-11 for fluorine-based FMZ PET

C-11 flumazenil (FMZ) PET has been found to have superior localizing specificity compared with F-18 FDG PET for patients with refractory focal epilepsy. However, there are logistical limitations inherent in the use of C-11. A promising potential alternative is F-18 FMZ, according to a study published July 15 in the Journal of Nuclear Medicine.

Lucy Vivash, MD, from the departments of medicine and neurology at the Melbourne Brain Centre, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia, and colleagues compared F-18 FMZ to F-18 FDG in epileptics and healthy controls using both quantitative and qualitative measures in this phase I/II study to find out how F-18 FMZ localized the epileptogenic zone in cases of drug-resistant temporal lobe epilepsy (TLE), the most common form of drug-resistant epilepsy in adults.

“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,” wrote Vivash et al.

The study included 17 F-18 FMZ and 20 F-18 FDG PET scans with healthy controls and both imaging methods for 12 patients with mesial temporal sclerosis and 19 with TLE. Images were coregistered using MR and a simplified reference tissue model was used to generate F-18 FMZ parametric binding potential. Quantification of both tracers was guided by statistical parametric mapping in the temporal lobe. Visual interpretation of images was masked.

F-18 FMZ PET was revealed to have a specificity of 94 percent, but a significantly lower sensitivity of 68 percent for the localization of the epileptogenic zone during visual interpretation of static standardized uptake with greater restriction of the area of abnormality than with FDG. F-18 FMZ falsely localized 10 percent of patients.

Regions of interest analysis showed lower FMZ binding potential in the ipsilateral hippocampus and such potential was independent of FDG uptake and hippocampal volume. In contrast, ipsilateral hippocampal F-18 FMZ volume correlated with FDG uptake. Findings from parametric mapping showed lower FDG uptake in 62 percent of patients and lower FMZ uptake in 45 percent of patients with smaller cluster sizes demonstrated in the latter from 160 to 37 voxels.

“The results agree with previous C-11 FMZ studies, with decreases in F-18 FMZ [binding potential] in the hippocampus, which are more marked on the epileptogenic side,” the authors wrote. “The region of decreased F-18 FMZ [binding potential] is more restricted than that of hypometabolism on F-18 FDG PET, indicating that it may provide a more specific localization of the epileptogenic zone. Further, the alterations in F-18 FMZ [binding potential] were independent of both F-18 FDG uptake and volumes, whereas the latter two were correlated, indicating that F-18 FMZ may provide a different and complementary measure of the epileptogenic substrate to these established clinical assessments. Importantly, the F-18 FMZ [binding potential] images could be constructed using a method that did not require arterial blood sampling, making it suitable for routine clinical practice.”

This trial was not intended to prove one radiotracer better compared to the other, but rather to build a reference point for further study in large clinical trials.