Detection of Focal Lesions in Epilepsy with [¹⁸F]UCB-H Synaptic Vesicle Protein 2A PET Imaging

Synaptic vesicle protein 2A (SV2A) is a universal marker of synaptic density. Recent advances in SV2A-targeted radiotracers have opened new windows into synaptic imaging. In focal epilepsy, synaptic dysfunction is a central pathologic feature. Unlike [¹⁸F]FDG PET, which reflects neuronal metabolism only indirectly, SV2A PET allows for direct quantification of synaptic density. We therefore evaluated [¹⁸F]UCB-H SV2A PET in comparison to [¹⁸F]FDG PET in patients with pharmacoresistant, unilateral focal epilepsy, aiming to assess its complementary value to established metabolic imaging. Methods: In total, 29 patients with unilateral focal epilepsy underwent both dynamic [¹⁸F]UCB-H PET (0-60 min) and static [¹⁸F]FDG PET (30-50 min) imaging. Eight patients were treated with the SV2A-binding medications levetiracetam or brivaracetam. [¹⁸F]UCB-H PET time-activity curves were extracted from 35 frames across cortical and subcortical regions, and Pearson correlation coefficients with [¹⁸F]FDG uptake were calculated for each frame to identify the most suitable imaging windows. Voxelwise percentage differences between epileptogenic and contralateral healthy hemispheres were computed to determine lesion severity and volume. Finally, we evaluated gaussian smoothing kernels for minimizing background noise while preserving contrast during lesion detection. Results: Treatment with SV2A-binding medications reduced late-phase [¹⁸F]UCB-H binding up to 75% compared with untreated individuals, demonstrating high target specificity. Framewise correlation analysis in unaffected contralateral hemispheres revealed significant associations between [¹⁸F]UCB-H and [¹⁸F]FDG uptake within the 0-10-min and 30-60-min postinjection intervals. These time windows were therefore selected for early- and late-phase analyses, respectively. Within epileptogenic foci, SV2A PET lesion severity correlated with [¹⁸F]FDG uptake for both early-phase (r = 0.61, P = 0.0042) and late-phase (r = 0.63, P = 0.0027) imaging. However, only early-phase SV2A PET lesion volume correlated with [¹⁸F]FDG lesion volume (r = 0.70, P = 0.0004), whereas late-phase SV2A PET volume did not. In line, [¹⁸F]FDG and early-phase [¹⁸F]UCB-H PET visually showed broad hypometabolic and hypoperfused areas around the epileptogenic zone, whereas late-phase [¹⁸F]UCB-H PET yielded sharper, high-contrast delineation of synaptic abnormalities. Conclusion: Dual-phase [¹⁸F]UCB-H PET provides complementary perfusion-like and synaptic information in focal epilepsy and shows spatial correspondence with [¹⁸F]FDG PET while offering more spatially confined synaptic signal changes.