NMDA-receptor Activity Visualized With (S)-[N-methyl-11C]ketamine and Positron Emission Tomography in Patients With Medial Temporal Lobe Epilepsy

Epilepsia. 1999 Jan;40(1):30-7. doi: 10.1111/j.1528-1157.1999.tb01985.x.

Abstract

Purpose: To determine whether neurochemical activation of the N-methyl-D-aspartate (NMDA) receptor-gated ion channel shows quantitative changes, measured as binding of 11C-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-11C]ketamine. The presurgical investigations included magnetic resonance imaging (MRI), PET with 18F-fluoro-deoxyglucose (18FDG), and seizure monitoring by using video-EEG. The uptake of (S)-[N-methyl-11C]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 18FDG.

Results: (S)-[N-methyl-11C]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-11C]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 18FDG.

Conclusions: Radioactivity uptake of intravenously administered (S)-[N-methyl-11C]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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carbon Radioisotopes / metabolism
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Electroencephalography / statistics & numerical data
  • Epilepsy, Temporal Lobe / diagnosis
  • Epilepsy, Temporal Lobe / diagnostic imaging*
  • Epilepsy, Temporal Lobe / metabolism*
  • Female
  • Fluorodeoxyglucose F18
  • Functional Laterality
  • Glucose / metabolism
  • Humans
  • Ketamine* / chemistry
  • Ketamine* / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Temporal Lobe / diagnostic imaging*
  • Temporal Lobe / metabolism
  • Thalamic Nuclei / diagnostic imaging
  • Thalamic Nuclei / metabolism
  • Tomography, Emission-Computed*
  • Videotape Recording

Substances

  • Carbon Radioisotopes
  • Receptors, N-Methyl-D-Aspartate
  • Fluorodeoxyglucose F18
  • Ketamine
  • Glucose