PET imaging of 5-HT1A receptor binding in patients with temporal lobe epilepsy.
ABSTRACT 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.
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.
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.
These findings support the hypothesis of reduced serotonin receptor binding in temporal lobe epileptic foci.
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ABSTRACT: The purpose of this paper is to discuss the mechanisms of α-[(11)C]methyl-L-tryptophan (AMT) PET as an in vivo biomarker for detection of epileptogenic cortex. AMT was originally designed as a tracer to measure the serotonin synthesis rate. This tracer was first applied in patients with medically refractory epilepsy in an attempt to detect changes in serotonin synthesis based upon reports of increased serotonergic innervation in cortical specimens obtained following epilepsy surgery. The first group of epilepsy patients undergoing AMT PET scans were patients with tuberous sclerosis complex. Studies of brain tissue subsequent to epilepsy surgery in these patients with tuberous sclerosis complex implicated the kynurenine pathway of tryptophan metabolism as a primary mechanism of increased brain tissue retention of AMT in epileptogenic brain regions, rather than alterations in serotonin synthesis. Kinetic analyses of AMT in brain tumors indicate changes in tryptophan transport and tissue retention in other pools as well. These studies indicate that AMT PET may be a biomarker of immune activation in the epileptogenic process.Biomarkers in Medicine 10/2011; 5(5):567-75. · 3.22 Impact Factor
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ABSTRACT: Serotonin and its various receptors are involved in numerous brain functions and neuropsychiatric disorders. The 5-HT1A family is the best characterized subtype of the fourteen currently known 5-HT receptors. The 5-HT1A receptor is closely involved in the pathogenesis of anxiety, depression, epilepsy and eating disorders and therefore is an important target for drug therapy. The development in the 1980s of molecules specifically targeting this receptor was followed by the rapid development of corresponding PET neuroimaging. Because this receptor represents a crucial target in neuroscience, a large number of radioligands have been developed by academic and industry centers for visualization and quantification, first in living animals and ultimately in humans. After a brief account of some of the structural and functional characteristics of brain 5-HT1A receptors, this review focuses on the main lines of evolution opened up by preclinical and clinical 5-HT1A PET radiopharmaceuticals, illustrating the potential value of PET for clinical research and drug development.Current Medicinal Chemistry 08/2013; · 4.07 Impact Factor
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ABSTRACT: Antidepresanların Epilepside Kullanım Alanları Özet Epilepsi beyindeki sinir hücrelerinin olağandışı, ani, aşırı ve anormal bir elekro-kimyasal boşalma yapması sonucu kısa süreli ortaya çıkan nörolojik bir hastalıktır. Epilepsi ile komorbit olarak ortaya çıkan depresyon epilepsisi olan hastaların yaşam kalitesini olumsuz etkileyebilir. Epilepsisi ve depresyo-nu olan insanlar depresyonu olmayan epilepsili hastalara nazaran, antiepilep-tik ilaçların yan etkilerine daha çok maruz kaldıklarından dolayı daha yaygın bir şekilde ilaca karşı direnç gösterirler. Epilepsideki duygu durum bozukluk-larının tedavisinde antiepileptik ve psikoaktif ilaçlar daha sık birlikte kullanıl-maya başlanmıştır. Farmakokinetik etkileşimler, ilacın emilim, dağılım, biyot-ransformasyon ve atılım gibi çeşitli aşamalarında meydana gelebilir. Epilep-sili hastalarda artmış depresyon riski mi yoksa depresyonlu hastalarda art-mış epilepsi riski mi sorusuna güncel bilgiler ışığında henüz net bir cevap ve-rilememiştir. Bu nedenle epilepsili hastalarda depresyon tedavisi önemle üze-rinde durulması gereken bir konu olarak karşımıza çıkmaktadır. Epilepsili has-talarda depresyon tedavisi yaparken ilaç seçiminde oldukça dikkatli olunma-lı, doz ayarı yapılırken küçük dozlarla başlayıp optimal doz titizlikle seçme-lidir. Son olarak antidepresanlar ile antiepileptik ilaçların gerek etki yerle-ri gerekse metabolizmaya uğradıkları yerler bakımında benzer oldukları için farmakodinamik ve farmakokinetik etkileşimlerinde çok dikkatli davranılma-sı gerekmektedir.Journal of Clinical and Analytical Medicine. 01/2012;