中文摘要：

目的 制备18 F-DPA-714,鉴定该标记化合物的标记率、放化纯、稳定性,并研究其在小鼠体内的生物学特性.方法 DPA-714以碳酸钾/K2.2.2溶液为相转移催化剂进行亲核取代反应.粗产物过铝柱预纯化,再经半制备HPLC分离,检测产品在PBS和血浆中的稳定性,测定其脂水分配系数（LogP）,分别在小鼠和大鼠体内进行生物分布及microPET显像研究.结果 18F-DPA-714的放化产率为31.6%（未衰变校正）,合成时间约为25 min,放化纯≥99%;在PBS和血浆中放置4 h,放化纯仍然≥99%.该标记化合物的LogP为2.71,其药代动力学更符合二室模型,分布半衰期T1/2α为2.40 min,消除半衰期T1/2β为69.15 min;主要分布在肺和肾脏,心脏次之,注射后30 min的放射性摄取值分别为（17.85±7.52）%ID/g、（15.41±1.80）%ID/g和（10.56±0.94）%ID/g.该标记化合物主要通过肝脏代谢、肾脏排泄,骨的摄取较稳定.正常老龄大鼠60 min动态扫描可见显像剂在脑实质内有摄取,清除缓慢.结论 本实验合成的18 F-DPA-714具有标记率高、合成时间短、前体用量少等优点,并具有良好的生物分布和血-脑屏障通透特性.

英文摘要：

Objective To synthesize 18 F-DPA-714 and to study its labeling rate, radiochemical purity, stability and biological characteristics. Methods 18F-was reacted with K2CO3/K2.2.2 and then en-gaged in nucleophilic substitution with DPA-714. The crude product was purified by aluminum column and semi-preparation HPLC. The stability of 18 F-DPA-714 was identified in PBS and plasma. The lipid-water partition coefficient （LogP） was determined. Biodistribution analysis and microPET imaging were performed on mice and rats respectively. Results It took about 25 min for synthesizing 18 F-DPA-714, the radiochemi-cal yield was 31.6% （decay not corrected）, and the radiochemical purity was ≥99%. The product re-mained stable within 4 h. The LogP of 18 F-DPA-714 was 2.71. Pharmacokinetics of 18 F-DPA-714 was more in line with the two compartment model, with the distribution half-life （ T1/2α） of 2.40 min and the elimina-tion half-life（ T1/2β） of 69.15 min. 18 F-DPA-714 was quickly uptaken by tissues after the tail vein injection. It mainly distributed in the lungs, kidneys, and heart, with the radioactive uptake values of （17.85±7.52）%ID/g, （15.41±1.80） %ID/g and （10.56±0.94） %ID/g at 30 min post-injection, respectively. 18F-DPA-714 was mainly metabolized through the liver, and excreted by the kidneys. The uptake in bones was stable. PET dynamic scanning showed that 18 F-DPA-714 accumulated in the brain of aged rats and cleared slowly within 60 min. Conclusions 18 F-DPA-714 prepared in this study has high labeling rate, short synthesis time and small precursor dosage. It displays good biological distribution and blood-brain barrier permeability characteristics.