Abstracts

Rationale: Positron emission tomography (PET) provides information on molecular processes involved in seizures, facilitating diagnostic and therapeutic approaches to epileptic disorders. PET imaging of glucose metabolism with [18F]2-fluoro-2-deoxy-D-glucose (FDG) has been clinically employed for identification of an epileptic focus, which can be visualized as a hypometabolic area. Meanwhile, an imaging agent producing a high contrast for epileptic changes is required for sensitive detection of the focus and delineation of its border. In the present study, we have conducted PET assays of EL mouse strain, a rodent model of idiopathic epilepsy in order to evaluate performance of [11C]1-methyl-L-tryptophan (1-MT), a novel PET tracer of tryptophan metabolism, in detection of epileptic changes, in light of mechanistic involvements of tryptophan and its metabolites in convulsions. In vivo assessments of [11C]1-MT have been made in comparison with [18F]FDG and tracers for neuroinflammation and glutamatergic transmission, which have also been implicated in epileptogenesis. Methods: EL mice with interictal state (n=14) and age-matched control ddY mice (n=6) were used in this study, and we examined three PET tracers including [11C]1-MT, metabotropic glutamate receptor 5 (mGluR5) ligand [11C]ABP688 and translocator protein 18kDa (TSPO) ligand [11C]Ac5216, which is a biomarker for neuroinflammation. [18F]FDG was also evaluated as a clinically available reference PET tracer. All PET scans were performed using small animal PET scanner, Focus220, and the mice were scanned for 90 minutes after intravenous injection of [11C]1-MT, [11C]ABP688 or [11C]Ac5216 via tail vein under inhalation of 1.5% isoflurane. [18F]FDG PET scans over 20 minutes were initiated at 50 minutes after tracer injection. The PET images and data were analyzed by PMOD image analysis software. Uptakes of [11C]1-MT and [18F]FDG in the brain were calculated as percentage of injected dose per volume. We also quantified binding potential (BPND) values of [11C]ABP688 and [11C]Ac5216 by employing cerebellum data as references. Results: In consistency with previous clinical findings, uptake of [18F]FDG in the EL mouse brain decreased by 21.6% compared to control mice(p < 0.05). In contrast, uptake of [11C]1-MT in the EL mouse brain increased by 69.2% compared to control mice (p < 0.0001). BPND values for [11C]ABP688 in the EL mouse neocortex, striatum, ventral hippocampus, and amygdala decreased by about 30% compared to ddY mice (p < 0.05). BPND values of [11C]Ac5216 in the EL mouse striatum increased by 15.4% compared to ddY mice (p < 0.05). Conclusions: Our results indicate that [11C]1-MT is the most promising PET tracer for discriminating between epileptic and normal brain regions with a higher contrast than [18F]FDG and other two PET tracers examined here. Funding: We didn't receive any funding for this abstract.