β-淀粉样斑块显像剂[^(18)F]FB-2的小鼠PET成像

PET imaging of mouse withβ-amyloid plaque imaging agent [^(18)F]FB-2

研究靶向脑内β-淀粉样斑块(Aβ斑块)的正电子发射断层显像(positron emission tomography,PET)显像剂[^(18)F]FB-2在小鼠体内的分布情况与PET成像效果。使用自制FB-OMs前体和Kryptofix 222标记合成[^(18)F]FB-2,并通过高效液相色谱(high performance liquid chromatography,HPLC)确认放化纯度;通过体内分布实验考察[^(18)F]FB-2在脑部的摄取与清除过程以及在其他组织器官的分布;[^(18)F]FB-2经尾静脉注射于Tg2576转基因小鼠和正常老龄小鼠,进行脑部动态PET成像,并通过成像脑的放射自显影确认[^(18)F]FB-2与脑内Aβ斑块的结合。标记合成的[^(18)F]FB-2放化纯度高;[^(18)F]FB-2一次性经尾静脉注射后,迅速透过血脑屏障进入脑内并较快地排出正常小鼠脑外;PET成像结果显示[^(18)F]FB-2在Tg2576小鼠脑内的放射性聚集明显高于正常老龄小鼠;成像脑放射自显影图中的黑点与硫黄素S染色的Aβ斑块位置一致。[^(18)F]FB-2有望成为用于临床阿尔茨海默病(Alzheimer’s disease,AD)早期诊断的新型PET显像剂。

To study the biodistribution and positron emission tomography(PET)imaging effect of[^(18)F]FB-2 imaging agent in vivo targetingβ-amyloid plaque(Aβplaque)in the brain of mice,[^(18)F]FB-2 was synthesized using self-made FB-OMs precursor and Kryptofix 222 maker,and its radiochemical purity was confirmed by high performance liquid chromatography(HPLC).The biodistribution experiments were performed to study the uptake and clearance of[^(18)F]FB-2 in the brain and its distribution in other tissues and organs.PET imaging was performed immediately after injection of[^(18)F]FB-2 into Tg2576 transgenic mouse and wild-type control.Ex vivo autoradiography was used to confirm the binding forβ-amyloid plaques in the brain.The results show that the radiochemical purity of labelled synthetic[^(18)F]FB-2 is high.[^(18)F]FB-2 rapidly enters the brain through the blood-brain barrier and rapidly discharges from the normal mouse brain after intravenous injection.PET image of Tg2576 mouse brain shows significantly higher accumulation of radioactivity than that in age-matched control and an excellent differentiation can be seen between them.Ex vivo autoradiograms confirm the specific binding ofβ-amyloid plaques in Tg2576 transgenic mouse brain.[^(18)F]FB-2 may be a useful PET probe for imagingβ-amyloid plaques in Alzheimer's disease(AD)brain tissue.