Head-to-Head comparison of [¹⁸F]FDG, [¹⁸F]FMZ, and [¹⁸F]SynVesT-1 positron emission tomography imaging in patients with drug-resistant epilepsy.

Abstract

The loss of synaptic vesicle glycoprotein 2 A (SV2A) can lead to dysfunction of GABAergic neurons, but a direct comparison of SV2A and GABA_A receptor densities in humans has not been assessed. This study evaluated SV2A and GABA_A receptor abnormalities in patients with drug-resistant epilepsy (DRE) and compared the patterns to glucose hypometabolism. Eleven patients with DRE were retrospectively recruited and underwent PET imaging with [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG), [¹⁸F]Flumazenil (FMZ), and [¹⁸F]SynVesT-1. Visual assessments counted abnormal metabolic brain regions based on the Anatomical Automatic Labeling (AAL) atlas, while voxel-level analyses delineated the abnormal metabolic distributions. The relationship between hypo-metabolic distributions and the age of epilepsy onset was analyzed. The hypometabolic regions in [¹⁸F]FDG PET, identified in the AAL atlas, was significantly broader than in [¹⁸F]FMZ (p = 0.0005) and [¹⁸F]SynVesT-1 (p = 0.0010) PET, with no statistical difference observed between [¹⁸F]FMZ and [¹⁸F]SynVesT-1 PET (p > 0.05). The voxel number in [¹⁸F]FDG PET was significantly higher than that of the [¹⁸F]FMZ and [¹⁸F]SynVesT-1 PET in both hypo-intensity area and severe hypo-intensity area. The ratio of the voxel number between these two area was higher for [¹⁸F]SynVesT-1 PET compared to [¹⁸F]FDG PET (p = 0.0195) and [¹⁸F]FMZ PET (p = 0.0237), and positively correlated with the age of epilepsy onset (r = 0.7397, p = 0.0145). [¹⁸F]FMZ and [¹⁸F]SynVesT-1 PET images revealed a more restricted pattern of reduced uptake compared to [¹⁸F]FDG PET in DRE patients. The age of epilepsy onset correlated with a reduction in [¹⁸F]SynVesT-1 uptake but not in [¹⁸F]FMZ or [¹⁸F]FDG uptake.