18F-SDM-8在大鼠颞叶癫痫模型中的显像研究

Imaging study of 18F-SDM-8 in rat temporal lobe epilepsy model

目的探讨靶向突触囊泡2A蛋白(SV2A)特异性显像剂(R)-4-(3-氟-5-(氟-18F)苯基)-1-((3-甲基吡啶-4-基)甲基)吡咯烷-2-酮(18F-SDM-8)是否可用于癫痫灶的检测。方法20只8~9周龄雄性Sprague-Dawley(SD)大鼠右侧海马内注射1.2μl海藻酸(癫痫组16只)或生理盐水(对照组4只)。在癫痫发作后1~2 d(急性期),6~7 d(潜伏期)和45~60 d(慢性期)对其进行18F-SDM-8和18F-FDG mircoPET/CT显像。计算不对称指数(AI)来评估18F-SDM-8 PET显像识别癫痫灶的能力。采用配对t检验、Mann-WhitneyU检验和Pearson相关分析数据。结果在18F-SDM-8的3个时期显像中,癫痫组和对照组的海马区AI差异均有统计学意义(z值:-2.64~2.67,均P<0.05)。2种显像剂在癫痫组中均有不对称摄取(右侧低于左侧),以右侧颞叶内侧降低为著,病理染色结果与显像结果一致。在癫痫组慢性期,18F-SDM-8在各感兴趣脑区右、左两侧的SUVmean差异均有统计学意义(t值:-33.40~-5.60,均P<0.05);2种显像剂在海马区域的不对称摄取具有较好的相关性(r=0.97,P=0.001),且该区域18F-SDM-8 AI[(34.2±8.4)%]比18F-FDG[(24.6±4.7)%]高1.4倍。结论18F-SDM-8 PET是测试SV2A水平的有前途的方法,可较好地反映海马内注射海藻酸诱发的大鼠癫痫模型中SV2A的变化情况,提高了分子显像对癫痫灶检测的灵敏度。

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 1.2μl 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 SUVmean(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.