Objective:To explore whether the specific synaptic vesicle glycoprotein 2A (SV2A) targeted imaging agent ( R)-4-(3-fluoro-5-(fluoro- 18F)phenyl)-1-((3-methylpyridin-4-yl)methyl)pyrrolidin-2-one ( 18F-SDM-8) can be used to detect epileptic foci. Methods:Twenty male Sprague-Dawley (SD) rats (8-9 weeks) were injected with 1.2 μl of kainic acid (16 rats in the epilepsy group) or saline (4 rats in the control group) into the right hippocampus. 18F-SDM-8 and 18F-FDG mircoPET/CT imaging were respectively performed at 1-2 d (acute phase), 6-7 d (incubation period) and 45-60 d (chronic phase) after the seizure. Asymmetric index (AI) was used to evaluate the epileptic foci identify ability of 18F-SDM-8. Paired t test, Mann-Whitney U test and Pearson correlation analysis were used to analyze data. Results:In the three periods of 18F-SDM-8 imaging, the differences of AI of hippocampus between the epilepsy group and control group were statistically significant ( z values: from -2.64 to 2.67, all P<0.05). Both imaging agents had asymmetric uptake in the epilepsy group (right was lower than left), and the decrease in the medial right temporal lobe was the most significant. The pathological staining results were consistent with the imaging results. In the chronic phase of the epilepsy group, the differences of 18F-SDM-8 SUV mean (right versus left) in each brain area of interest were statistically significant ( t value: from -33.40 to -5.60, all P<0.05). The asymmetric uptake of the two imaging agents in the hippocampus had a better correlation ( r=0.97, P=0.001), and the AI of 18F-SDM-8 ((34.2±8.4)%) in this area was 1.4 times higher than that of 18F-FDG ((24.6±4.7)%). Conclusions:18F-SDM-8 PET is a promising method to test the level of SV2A. It can reflect the changes of SV2A in the rat epilepsy model induced by intrahippocampal injection of kainic acid, and improve the sensitivity of molecular imaging for epileptic foci.