α-[11C] methyl-L tryptophan-PET as a surrogate for interictal cerebral serotonin synthesis in migraine without aura

Abstract

Alteration in central serotonin biology has been implicated in migraine, and serotonin (5-HT) agonists have been available for more than a decade in the treatment of that condition. To test this hypothesis, we studied invivo using positron-emission tomography (PET) and α-[(11)C] methyl-L-tryptophan (α-[(11)C]MTrp) as a surrogate marker of cerebral 5-HT synthetic rate before and after administration of eletriptan in migraine and control subjects. Six nonmenopausal female migraine subjects with migraine without aura (MoA) and six nonmenopausal age-matched female control subjects were scanned at baseline and after oral administration of 40 mg of eletriptan. Migraine subjects at the time of PET had to have been headache free for a minimum of three days. Images of (α-[(11)C]MTrp) brain trapping were colocalized with individual MRI images in three dimensions and analyzed. There was no difference in baseline cerebral global 5-HT synthesis between migraine and control subjects. After administration of eletriptan, there was a striking global reduction in cerebral 5-HT synthesis (K*) in the migraine group and in 22 regions of interest (ROIs). In control subjects, no significant changes were found in global cerebral 5-HT synthesis (K*) or in any of the ROIs. These findings suggest in migraine an interictal alteration in the regulation mechanisms of cerebral 5-HT synthesis.