NMDA‐Receptor Activity Visualized with (S)‐[N‐Methyl‐11C]Ketamine and Positron Emission Tomography in Patients with Medial Temporal Lobe Epilepsy

Purpose : To determine whether neurochemical activation of the N-methyl-D-aspartate (NMDA) receptor-gated ion channel shows quantitative changes, measured as binding of 1 C-labeled (S)-[N-methyl]ketamine, in patients with medial temporal lobe epilepsy (MTLE). Methods: Eight patients with MTLE who were evaluated regarding epilepsy surgery underwent positron emission tomography (PET) with (S)-[N-methyl- 11 C]ketamine. The presurgical investigations included magnetic resonance imaging (MRI), PET with 18 F-fluoro-deoxyglucose ( 18 FDG), and seizure monitoring by using video-EEG. The uptake of (S)-[N-methyl- 11 C]ketamine in the temporal lobe of ictal onset was compared with the contralateral side and correlated to changes in regional glucose metabolism measured by PET with 18 FDG. Results: (S)-[N-methyl- 11 C]ketamine rapidly reached the brain, and high radioactivities were measured in the striatum. thalamic nuclei, and cortical regions. Overall the brain uptake and regional binding potentials of (S)-[N-methyl- 11 C]ketamine were similar to measurements observed previously in healthy controls. However, 20 min after administration, when blood flow influence was negligible, a side-to-side comparison revealed a 9-34% reduction of tracer radioactivity in the temporal lobes of ictal onset. At earlier times, the differences in binding potentials were less pronounced, 9-21%. The magnitude and distribution of the reduction were similar to the metabolic pattern seen on PET scans with 18 FDG. Conclusions: Radioactivity uptake of intravenously administered (S)-[N-methyl- 11 C]ketamine was reduced in temporal lobes of ictal in patients with TLE. This may reflect reduced NMDA-receptor density, reduced perfusion, focal atrophy, or other factors.