脑灌注显像剂99Tcm-MPBDA的研制与动物实验

目的 研制一种新的SPECT脑灌注显像剂。方法 将化学合成的N2S三齿配体2－巯基丙基－1，2－苯二胺（MPBDA）用^99Tc^m标记：25只昆明种小白鼠静脉注射100μL555-740kBq^99Tc^m-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218．3－333MBq^99Tc^mMPBDA或^99Tc^m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 ^99Tc^m－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^99Tc^m－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^99Tc^m－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^99Tc^m－MPBDA后均无毒副反应。结论 研制的^99Tc^m－MPBDA具有^99Tc^m－ECD相近的脑血流灌注显像性能，用于活体安全可靠。

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

Objective　To investigate a novel potential SPECT cerebral blood flow perfusion imaging agent. Methods　N2S 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 Ty2<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.