脑灌注显像剂^(99)Tc^m-MPBDA的研制与动物实验

Preparation and animal studies of a novel potential cerebral perfusion imaging agent

目的 研制一种新的SPECT脑灌注显像剂。方法 将化学合成的N2 S三齿配体 2 巯基丙基 1,2 苯二胺 (MPBDA)用99Tcm 标记 ;2 5只昆明种小白鼠静脉注射 10 0 μL 5 5 5～ 740kBq99Tcm MPBDA ,进行体内生物分布实验 ;2只健康恒河猴 (4～ 6kg)静脉快速注入 2 18.3～ 333MBq99Tcm MPBDA或99Tcm 双半胱乙脂 (ECD)后分别即刻连续动态采集和给药后 70min行全身显像和脑断层显像 ;2组小鼠和 3只家兔分别进行了急性毒理和热原实验。结果 99Tcm MPBDA的产率和放化纯度分别大于95 %和 97%。小鼠体内分布实验结果表明99Tcm MPBDA能在脑内浓聚并具有很好的脑滞留 ,血清除半衰期小于 15min。猴脑动态血流灌注显像示注药后 2min脑放射性达高峰 ,1h脑放射性占 2min的 83.0 % ,70min后入脑量高达 2 .76 %ID ,略低于99Tcm ECD(2 .9%ID)。断层显像可见大脑灰白质对比度好 ,影像轮廓较清晰。小鼠和兔子注射99Tcm MPBDA后均无毒副反应。结论 研制的99Tcm MPBDA具有与99Tcm ECD相近的脑血流灌注显像性能 ,用于活体安全可靠。

Objective To investigate a novel potential SPECT cerebral blood flow perfusion imaging agent. Methods N 2S tridentated α-mercapto-propyl-1,2-benzenediamine (MPBDA) was obtained from chemical synthesis IR and was labeled with 99Tcm.Biodistribution analysis in 25 mice was performed after intravenous injection of 100 μL 555～740 kBq of 99Tcm-MPBDA. Dynamic acquisition was performed after rapid intravenoues injection of 218.3～333 MBq 99Tcm-MPBDA or 99Tcm-ECD,while whole body imaging and brain perfusion imaging were done after 70 min in 2 normal monkeys.Preclinical studies including toxicity and pyrogen tests in mice and rabbits were undertaken.Results The radiochemical synthetic yield and radiochemical purity of MPBDA labeled with 99Tcm were more than 95% and 97%, respectively. Mice biodistribution test showed the 99Tcm-MPBDA can concentrate in brain with good retention,and blood clearance Ty 2<15 min. Brain dynamic perfusion imaging in monkey demonstrated that radioactivity reached peak value in brain after 2 min,radioactivity in brain after 1 h was 83% of 2 min.Brain radioactivity reached as high as 2.76 %ID after 70 min,slightly lowered than that of 99Tcm-ECD (2.9%ID).SPECT imaging of cerebral gray and white matter showed good contrast with a clear contour.No toxic side affect in mice and rabbits after 99Tcm-MPBDA injection was found.Conclusion Investigated 99Tcm-MPBDA has almost the same property as 99Tcm-ECD.It is safe and reliable in vivo.