18F-DPA-714的制备及其在动物体内的生物学分布  

Preparation of 18 F-DPA-714 and its biodistribution in rodents

作　　者：胡伟 赵军 杨敏[2] 管一晖 左传涛 华逢春 潘栋辉[2] Hu Wei Zhao Jun Yang Min Guan Yihui Zuo Chuantao Hua Fengchun Pan Donghui(Department of PET Center, Huashan Hospital, Fudan University, Shanghai 200235, Chin Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China)

机构地区：[1]复旦大学附属华山医院PET中心,上海200235 [2]江苏省原子医学研究所,无锡214063

出　　处：《中华核医学与分子影像杂志》2017年第10期632-636,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家重点研发计划（2016YFC1306600）;国家自然科学基金（81371625）

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.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.

关 键 词：DPA-714 同位素标记 氟放射性同位素 正电子发射断层显像术 小鼠 大鼠 DPA-714 

分 类 号：R817[医药卫生—影像医学与核医学]