Abstracts

Substance P (SP) is a neuropeptide that exerts its biological effect through binding to the neurokinin 1 (NK1) receptor. Substance P has been shown to facilitate glutaminergic excitatory synaptic transmission. In animal models, intrahippocampal injections of SP induce status epilepticus and histopathological damage resembling hippocampal sclerosis in man. This suggests that the activation of NK1- receptors could play a part in the generation of limbic seizures and related pathology.
The high affinity and selective NK1-receptor antagonist ¹¹C-GR205171 has been shown to be suitable for in vivo characterisation of NK1-receptor binding using positron emission tomography.
The aim of this study was to explore whether there is altered NK1 receptor distribution in patients with TLE using PET with ¹¹C-GR 205171. We performed positron emission tomography (PET) with ¹¹C-GR205171 in five patients, all female, with TLE undergoing evaluation for epilepsy surgery. All patients had mesiotemporal sclerosis defined by MRI and seizure onset zone was confirmed with ictal video-EEG.
Summation images were obtained by adding together images acquired in the time interval 20-55 min after injection. In these images, regions of interest were manually generated to represent 15 different areas of the brain. All regions delineated sufficiently small to be representative for radioactivity concentration for respective region. Cerebellum was used as a reference region utilizing the Patlak graphical method. With this method, linear graphs were made suggesting slow dissociation from the binding site.
Transaxial and coronal images were made and analysed by visual inspection and manually drawn regions of interest. Contralateral homologous regions served as control and asymmetry index were calculated with the formula: (R-L)*200/(R+L). A substantial reduction of the binding of ¹¹C-GR 205171 was seen in the affected temporal lobe in two patients and in two patients there was an increased tracer uptake. In the fifth patient the result were ambiguous. In this pilot study with PET with ¹¹C-GR 205171, an NK-receptor antagonist, no uniform uptake pattern of the tracer was seen. Further evaluation with a more refined methodology, including voxel-based statistical analysis may improve the accuracy of the method.