诊断学理论与实践 ›› 2022, Vol. 21 ›› Issue (04): 482-489.doi: 10.16150/j.1671-2870.2022.04.011
屈骞1, 海汪溪1, 胡生焰2, 张敏1, 陈肖玥1, 周熠磊1, 王瑾1, 胡晓平2, 李彪1, 胡佳佳1()
收稿日期:
2022-02-20
出版日期:
2022-08-25
发布日期:
2022-11-07
通讯作者:
胡佳佳
E-mail:hjj11592@rjh.com.cn
基金资助:
QU Qian1, HAI Wangxi1, HU Shengyan2, ZHANG Min1, CHEN Xiaoyue1, ZHOU Yilei1, WANG Jin1, HU Xiaoping2, LI Biao1, HU Jiajia1()
Received:
2022-02-20
Online:
2022-08-25
Published:
2022-11-07
Contact:
HU Jiajia
E-mail:hjj11592@rjh.com.cn
摘要:
目的:验证AllinOne模块自动化制备多巴胺转运蛋白(dopamine transporters,DAT)显像探针18氟-氮-(3-氟丙基)-2β-甲酯基-3β-(4′-碘苯基)去甲基托烷[18F-N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4′-iodophenyl) nortropane,18F-FP-CIT]的稳定性和效率,同时验证产物的安全性和靶向性及对大鼠基底节区的显像作用。方法:以氮-(3′-甲基黄酰氧基丙基)-2β-甲酯基-3β-(4′-碘苯基)去甲托烷作为反应前体,在四丁基氢氧化铵(Tetrabutylammonium Hydroxide,TBAOH)和氨基聚醚(Aminopolyether,Kryptofix 222)催化下,与干燥后的18氟离子(18F-)发生氟化反应,产物经高效液相色谱法(high performance liquid chromatography,HPLC)分离纯化,并以最高产率条件建立AllinOne模块的18F-FP-CIT自动化合成程序,并对产物行质量控制检测和大鼠脑微型正电子发射计算机断层扫描系统(micro positron emission computed tomography,Micro PET/CT)显像验证。结果:由AllinOne模块自动化制备的20批次18F-FP-CIT的平均合成时间为(72.9±8.9) min,经衰减校正后,合成平均效率为34.8%±5.7%,平均放射化学纯度为98.4%±2.0%。产物18F-FP-CIT的无菌检测、内毒素检测、毒性检测结果以及溶剂残留乙腈含量均符合临床使用标准。Micro PET/CT显像可见正常大鼠基底节均匀、明显的靶向摄取,基底节摄取18F-FP-CIT的程度分别是大脑皮层的2.6倍,小脑的3.7倍,颅骨的4.1倍。结论:AllinOne模块可稳定、迅速、高质地自动化制备DAT显像剂18F-FP-CIT,有望为帕金森病(Parkinson′s disease,PD)等神经退行性变的临床诊疗提供影像技术支持。
中图分类号:
屈骞, 海汪溪, 胡生焰, 张敏, 陈肖玥, 周熠磊, 王瑾, 胡晓平, 李彪, 胡佳佳. 多巴胺转运蛋白显像探针18F-FP-CIT的AllinOne模块自动化制备及大鼠基底节Micro PET/CT显像[J]. 诊断学理论与实践, 2022, 21(04): 482-489.
QU Qian, HAI Wangxi, HU Shengyan, ZHANG Min, CHEN Xiaoyue, ZHOU Yilei, WANG Jin, HU Xiaoping, LI Biao, HU Jiajia. Automated synthesis of dopamine transporters imaging probe 18F-FP-CIT based on allin one for Micro PET/CT imaging of rat basal ganglia[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(04): 482-489.
图2
应用AllinOne化学合成模块一步法自动化合成18F-FP-CIT的示意图 注:图中1号位为接H218O靶废液(含18F-原液)的收集瓶(垂直位)/气压阀(水平位);2号位为含18F-洗脱液的BD注射器(3 mL);3号位为含HPLC溶液的西林瓶(15 mL);5号位为PS-HCO3-柱(通过聚乙烯管连接至4号位);6号位为接收18F-的注射器(20 mL);7号位为接进样管的反应瓶(垂直位)/接反应瓶进气管的气压阀(水平位);8号位为含前体溶液的BD注射器(3 mL);9号位为接收HPLC分离产物的西林瓶(50 mL);10号位为接收HPLC分离产物的收集端;11号位为鲁尔锁注射器(20 mL);13号位为C18柱(通过聚乙烯管连接至12号位);14号位为含乙醇的西林瓶(15 mL);15号位为注射用水袋;16号位为接收反应化合物至进样环的载入端;17号位为含生理盐水溶液的西林瓶(20 mL);18号位为连接接收终产品的西林瓶(垂直位)/气压阀(水平位)。
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