PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy.
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-HT1A 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-HT1A 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.


CONCLUSIONS
These findings support the hypothesis of reduced serotonin receptor binding in temporal lobe epileptic foci.
Toczek
M T
MT
Clinical Epilepsy Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, Warren Grant Magnuson Clinical Center, NIH, Bethesda, MD 20892-1408, USA.
Carson
R E
RE
Lang
L
L
Ma
Y
Y
Spanaki
M V
MV
Der
M G
MG
Fazilat
S
S
Kopylev
L
L
Herscovitch
P
P
Eckelman
W C
WC
Theodore
W H
WH
D000328:Adult; D001284:Atrophy / Q000175:diagnosis; D002560:Cerebrovascular Circulation; D004833:Epilepsy, Temporal Lobe / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D013702:Temporal Lobe / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
C435829:N-(2-(4-(2-methoxyphenyl)piperazino)ethyl)-N-2-(pyridyl)-4-fluorocyclohexanecarboxamide; D010879:Piperazines; D011725:Pyridines; D044282:Receptor, Serotonin, 5-HT1A; D005947:Glucose