Cortical abnormalities of synaptic vesicle protein 2A in focal cortical dysplasia type II identified in vivo with (18)F-SynVesT-1 positron emission tomography imaging

PURPOSE: The loss of synaptic vesicle glycoprotein 2A (SV2A) is well established as the major correlate of epileptogenesis in focal cortical dysplasia type II (FCD II), but this has not been directly tested in vivo. In this positron emission tomography (PET) study with the new tracer (18)F-SynVesT-1, we evaluated SV2A abnormalities in patients with FCD II and compared the pattern to (18)F-fluorodeoxyglucose ((18)F-FDG). METHODS: Sixteen patients with proven FCD II and 16 healthy controls were recruited. All FCD II patients underwent magnetic resonance imaging (MRI) and static PET imaging with both (18)F-SynVesT-1 and (18)F-FDG, while the controls underwent MRI and PET with only (18)F-SynVesT-1. Visual assessment of PET images was undertaken. The standardized uptake values (SUVs) of (18)F-SynVesT-1 were computed for regions of interest (ROIs), along with SUV ratio (SUVr) between ROI and centrum semiovale (white matter). Asymmetry indices (AIs) were analyzed between the lesion and the contralateral hemisphere for intersubject comparisons. RESULTS: Lesions in the brains of FCD II patients had significantly reduced (18)F-SynVesT-1 uptake compared with contralateral regions, and brains of the controls. (18)F-SynVesT-1 PET indicated low lesion uptake in 14 patients (87.5%), corresponding to hypometabolism detected by (18)F-FDG PET, with higher accuracy for lesion localization than MRI (43.8%) (P < 0.05). AI analyses demonstrated that in the lesions, SUVr for each of the radiotracers were not significantly different (P > 0.05), and (18)F-SynVesT-1 SUVr correlated with that of (18)F-FDG across subjects (R(2) = 0.41, P = 0.008). Subsequent visual ratings indicated that (18)F-SynVesT-1 uptake had a more restricted pattern of reduction than (18)F-FDG uptake in FCD II lesions (P < 0.05). CONCLUSION: SV2A PET with (18)F-SynVesT-1 shows a higher accuracy for the localization of FCD II lesions than MRI and a more restricted pattern of abnormality than (18)F-FDG PET. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00259-021-05665-w.