【摘要】 目的:探讨国内研制的“一步法”药盒标记的多巴胺转运蛋白(DAT)显像剂99mTc-TRODAT-1在动物体内的生物学特性和显像效果。方法:①“一步法”药盒生产标记物;②正常大鼠体内生物分布特性的实验;③正常猴和偏侧PD模型猴给药后3h脑SPECT显像。结果:①TRODAT-1药盒标记简便。经TLC检测,标记率为79.9%,室温下放置2.5h稳定;②正常大鼠体内放射性清除迅速,主要由肝脏代谢后经肠道排出体外;③99mTc-TRODAT-1脑内浓聚较低,但纹状体(ST)区放射性摄取快速且保留较好,小脑(CB)清除较快,ST/CB值于2h达峰值(ST/CB=3.21),持续4h;④纹状体对99mTc-TRODAT-1的特异性摄取不受预先注射的氟哌啶醇的影响;⑤99mTc-TRODAT-1在大鼠体内分布无性别差异;⑥猴脑DATSPECT显像能基本清晰显示双侧ST正常影像及其病理改变。ST/CB值可以作为反映ST特异性摄取的参数指标。结论:“一步法”药盒制备的99mTc-TRODAT-1可用于脑SPECT显像研究,显像时间取给药后2~3h时间段为宜。更多还原

【Abstract】 Objective:To investigate the pharmacological characteristics of ^99mTc-TRODAT-1 as an imaging agent for dopamine transporter.Methods:①One-vial formulation produced label imaging agent in China;②Biodistribution in rats;③Imaging in normal and hemi-parkinsonian model monkeys. Results:①The radiochemical purity of ^99mTc-TRODAT-1 was about 79.9% evaluated by TLC.It was stable for 2.5 hours at room temperature;②The clearance of ^99mTc-TRODAT-1 in the blood of rats is fast.The major radioactivity is excreted by hepatobiliary system;③The brain uptake was moderate.But the agent high-affinity bind to DAT which is highly concentrated in striatal area and there is no specific uptake in cerebellum.The ratio of ST/CB is high;④Pretreatment with haloperidol,a no competing ligand,did not result in any significant change in the level of striatal uptake;⑤The distribution pattern as well as the brain regional uptake of ^99mTc-TRODAT-1 did not display any significant difference between male and female rats at 60 min postinjection;⑥The monkeys’ SPECT images can clearly display the normal uptake and the pathologic changes in striatal area at 3 hour postinjection.The semi quantitative analysis-ST/CB can reveal the specific uptake value for ^99mTc-TRODAT-1 in reflecting the numeral and functional changes in DAT. Conclusion:^99mTc-TRODAT-1 labeled by one-vial formulation of China can be the imaging agent of DAT in clinical study.It proves to be effective and promising radiopharmaceuticals in vivo assessment of the loss of dopamine neurons in Parkinson’s disease and other neurodegenerative disease.更多还原