PET imaging of 5-HT_1A receptor binding in patients with temporal lobe epilepsy

Abstract

Background: Activation of central serotonin (5-HT)_1A receptors, found in high density in brainstem raphe, hippocampus, and temporal neocortex, exerts an anticonvulsant effect in various experimental seizure models. To test the hypothesis that 5-HT_1A receptor binding is reduced in human epileptic foci, PET imaging was performed using the radioligand [¹⁸F]trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl)cyclohexanecarboxamide ([¹⁸F]FCWAY), a selective 5-HT_1A receptor antagonist, in patients with temporal lobe epilepsy and normal controls.

Methods: MRI and PET were performed using [¹⁵O]water and [¹⁸F]FCWAY in 10 controls and in 12 patients with temporal lobe epilepsy confirmed on ictal video-EEG; patients also underwent [¹⁸F]fluorodeoxyglucose PET. Using quantitative PET image analysis, regional values were obtained for [¹⁸F]FCWAY volume of distribution (V), cerebral blood flow (CBF), and glucose cerebral metabolic rate (CMRglc). Hippocampal volume (HV) was also measured with MRI. [¹⁸F]FCWAY V PET and MR measures were compared within patients and controls using paired t-tests; grouped comparisons were made with two sample t-tests.

Results: Lower [¹⁸F]FCWAY V was found ipsilateral than contralateral to the epileptic focus in inferior medial (IMT) and lateral (ILT) temporal regions of patients (ILT 47.4 ± 6.1 vs 61.8 ± 6.1, p < 0.01; IMT 52 ± 4.6 vs 67.0 ± 6.0, p < 0.01). [¹⁸F]FCWAY V was 29% lower in raphe and 34% lower in the ipsilateral thalamic region of patients than controls. In ILT, mean [¹⁸F]FCWAY V asymmetry index (AI) was significantly greater than mean CBF and mean CMRglc AI. Mean [¹⁸F]FCWAY V AI in IMT was greater than mean HV AI, but the difference was not significant.

Conclusion: These findings support the hypothesis of reduced serotonin receptor binding in temporal lobe epileptic foci.