论文部分内容阅读
目的:观察n 18F-T807显像剂的安全性及其在阿尔茨海默病(AD)模型小鼠和正常老龄化小鼠体内的生物学分布。n 方法:选取无特定病原体级7月龄雄性昆明小鼠20只,体质量(22±2)g;10月龄雄性tau-转基因(appsw-tau,野生型/半合子)小鼠10只,体质量(34±2)g;10月龄雄性野生型C57BL/6J小鼠25只,体质量(28±2)g。将20只昆明小鼠采用随机数表法随机分成4组用于急性毒性实验,每组5只。对其中3组的小鼠分别尾静脉注射由1 ml生理盐水稀释的3.7 MBq、18.5 MBq、37 MBqn 18F-T807显像剂,对第4组小鼠尾静脉注射1 ml生理盐水作为对照组。连续14 d观察小鼠的状态和体质量变化情况。将15只野生型C57BL/6J小鼠用于生物分布实验。取由200 μl生理盐水稀释的250 μCin 18F-T807显像剂经尾静脉注入体内,给药后5、15、30 min眼球取血500 μl并脱颈处死。分离血浆和红细胞,并测量心、肝、脾、肺、肾、脑、肌肉的质量,计算每克组织放射性摄取百分数。将tau-转基因(appsw-tau,野生型/半合子)小鼠作为AD模型小鼠,野生型C57BL/6J小鼠作为正常老龄化小鼠,各10只。釆用GE SIGNA正电子发射断层显像(PET)/MRI联合扫描仪行n 18F-T807 PET/MRI全身显像。n 结果:急性毒性实验结果表明,最大耐受量下n 18F-T807显像剂对小鼠的生长无不良影响。生物分布实验结果表明,n 18F-T807从脑中迅速清除,肾排泄是一个重要的清除途径。AD模型小鼠与正常老龄化小鼠的PET/MRI显像结果表明,AD模型小鼠脑内放射性聚集高于正常老龄化小鼠,但差异无统计学意义(n P=0.142)。n 结论:18F-T807显像剂安全有效,该显像剂经消化系统和泌尿系统代谢,可快速穿透正常及转基因型痴呆小鼠的血脑屏障,并迅速洗脱。n “,”Objective:To observe the safety and efficacy of n 18F-T807 imaging agent and its biological distribution in Alzheimer′s disease(AD)model mice and normal aging mice.n Methods:Twenty specific pathogen free 7-months-old male Kunming mice with body weight of(22±2)g, ten 10-months-old male Tau transgenic(appsw-tau, wild type/hemizygous)mice with body weight of(34±2)g, twenty-five 10-months-old male wild-type C57BL/6J mice with body weight of(28±2)g were selected.Twenty Kunming mice were randomly with the random number table method divided into 4 groups with 5 mice in each group for acute toxicity test.Mice in 3 groups were injected with 3.7 MBq, 18.5 MBq and 37 MBQ n 18F-T807 imaging agents diluted by 1 ml normal saline into the caudal vein, respectively.Mice in the fourth group were injected with 1 ml normal saline as the control group.The state and body weight of mice were observed for 14 days.Fifteen wild-type C57BL/6J mice were used for biological distribution experiment, 250 μCi n 18F-T807 imaging agent diluted by 200 μl normal saline was injected into the body through the tail vein, and 500 μl blood was taken from the eyeballs at 5, 15 and 30 minutes after administration, and the mice were killed.The plasma and red blood cells were separated, and the heart, liver, spleen, lung and kidney were weighed, and the percentage of radioactive uptake per gram of tissue was calculated.Tau transgenic(APPSW-Tau, wild-type/semi-zygous)mice were used as AD model mice, and wild-type C57BL/6J mice were used as normal aging mice, 10 in each group.GE SIGNA positron emission tomography(PET)/MRI Scanner was adopted for n 18F-T807 PET/MRI body imaging.n Results:The results of acute toxicity test showed that n 18F-T807 imaging agent had no adverse effect on the growth of mice at the maximum tolerated dose.The results of biological distribution showed that n 18F-T807 was rapidly cleared from the brain, and renal excretion was an important pathway.PET/MRI imaging results of AD model mice and normal aging mice showed that the radioactive accumulation in the brain of AD model mice was higher than that of normal aging mice, but the difference was not statistically significant(n P=0.142).n Conclusions:The imaging agent n 18F-T807 is safe and effective.The imaging agent is metabolized by digestive and urinary systems and can rapidly penetrate the blood-brain barrier and quickly elute in normal and transgenic dementia mice.n