18F-fluorodeoxyglucose and 18F-flumazenil positron emission tomography in patients with refractory epilepsy

Epilepsy is a neurological disorder characterized by epileptic seizures as a result of excessive neuronal activity in the brain. Approximately 65 million people worldwide suffer from epilepsy; 20-40% of them are refractory to medication therapy. Early detection of disease is crucial in the management of patients with epilepsy. Correct localization of the ictal onset zone is associated with a better surgical outcome. The modern non-invasive techniques used for structural-functional localization of the seizure focus includes electroencephalography (EEG) monitoring, magnetic resonance imaging (MRI), single photon emission tomography/computed tomography (SPECT/CT) and positron emission tomography/computed tomography (PET/CT). In recent years, multiple studies have demonstrated that 2-deoxy-2-[ 18 F]fluoro-D-glucose ( 18 F-FDG) PET/CT can predict surgical outcome in patients with refractory epilepsy. Unfortunately, 18 F-FDG is not an ideal PET tracer regarding the management of patients with epilepsy: areas of glucose hypometabolism do not correlate with the proven degree of change within hippocampal sclerosis, as observed by histopathology or MRI. In the 1980s, Flumazenil was proposed as a promising new marker for imaging of benzodiazepine receptors by PET.  Flumazenil blocks the benzodiazepine sites on GABA A receptors and thus antagonizes the action benzodiazepines have on the central nervous system. The substance was initially labelled with Carbon-11 ( 11 C-FMZ).  However, use of 11 C-FMZ in clinical practice has been limited by its short half-life and necessitating an on-site cyclotron for production. [18F]flumazenil ( 18 F–FMZ) has been established as the tracer of choice for patients with refractory epilepsy in some neurological centres in Europe. Multiple new PET tracers for presurgical evaluation of patients with epilepsy are still under preclinical investigations.