Abstracts

Rationale: Objective: To report the first known epilepsy patient who underwent in vivo imaging of synaptic vesicle glycoprotein 2A (SV2A) using a novel PET radioligand 11C-UCB-JMethods: Background: Resective surgery is most frequently the only alternative available to achieve seizure freedom in patients experiencing drug-resistant epilepsy. In patients where MRI shows no lesion, information obtained from functional imaging techniques is particularly important to plan the placement of subdural electrodes for invasive monitoring. Because 18F-FDG PET usually shows a large area of hypometabolism extending beyond the epileptogenic zone and the localization value in extra temporal lobe epilepsies is low, new PET radiotracers that could more accurately identify the epileptogenic zone are needed. Synaptic vesicle glycoprotein 2A (SV2A) is an essential vesicle membrane protein which is located ubiquitously in synapses in the central nervous system. Clinical and experimental data have suggested that SV2A is involved in epilepsy with decreased SV2A receptor density found in the epileptogenic zone. In addition, levetiracetam and its analogs appear to exert their anticonvulsant effect through SV2A. We recently developed 11C-UCB-J as a promising radioligand for quantitative measurement of SV2A with positron emission tomography (PET). Our first in human SV2A PET studies in healthy subjects have shown that 11C-UCB-J has high brain penetration, good plasma free fraction, and moderate peripheral metabolism. The kinetic profile allowed for excellent test/retest reliability and the production of high-quality parametric images making this a potentially excellent PET tracer for quantitative imaging of SV2A in the human brain.Results: Case Description: A 52 year old male with mild intellectual disability and intractable epilepsy since 11 months of age. He underwent Video EEG monitoring that captured seizures emanating from the right temporal region and MRI imaging that showed right mesial temporal sclerosis (MTS). He was thought to be a good candidate for right temporal lobectomy. PET imaging showed significant reduction of 11C-UCB-J binding in the right mesial temporal lobe colocalized with the MTS seen on MRI. A month later, he underwent a right anterior mesial temporal lobectomy without any complications. Immunohistochemistry showed decrease expression of SV2A in the surgically removed hippocampus compared to an autopsy control. He remains seizure free for the last 4 months since the lobectomy.Conclusions: We report the first epilepsy case with quantitative imaging of SV2A using a novel PET radiotracer. Decreased binding of 11C-UCB-J in the right mesial temporal lobe was validated with decreased expression of SV2A in the surgically removed hippocampus. We believe that 11C-UCB-J has the potential to be diagnostically useful for seizure focus determination in epilepsy patients although further studies, including a comparison with 18F-FDG, are needed.