自动化“点击合成”正电子标记肽类细胞凋亡显像剂^(18)F-Pen-peptide  

Automated "click chemistry" synthesis of ^(18)F-Pen-peptide as an apoptosis imaging agent

作　　者：张锦明[1] 张晓军[1] 张宝石[2] 刘健[1] 王卉[1] 孙志军[1] 田嘉禾[1] 

机构地区：[1]解放军总医院核医学科,北京100853 [2]解放军总医院第一附属医院胸心外科,北京100048

出　　处：《核技术》2011年第11期845-850,共6页Nuclear Techniques

基　　金：国家自然科学基金项目(81771400;81071170)资助

摘　　要：采用国产双管PET-MF-2V-IT-1型多功能模块,在第一反应管合成6-氟-18戊炔,将之蒸发到第二反应管,与叠氮短肽前体在亚铜催化下发生点击反应,在室温下生成18F-Pen-peptide,经半制备HPLC纯化,再经固相萃取得到注射18F-Pen-peptide。采用A549肺腺癌细胞测量行化疗前后的细胞摄取。结果显示,6-氟-18戊炔合成效率为51%,6-氟-18戊炔与叠氮前体的反应效率近99%,总的合成效率为(21.0±4.5)%(n=6,未校正),合成时间为70 min。最终产品的放射性活度14.8–22.2 GBq,放化纯为99%,比活度为870 GBq/μmol。A549细胞摄取实验表明,未化疗的细胞对18F-Pen-peptide摄取为(0.06±0.01)%,细胞凋亡为(1.02±0.31)%。化疗24 h后A549细胞摄取值为(0.86±0.04)%,细胞凋亡为(10.23±2.43)%。18F-Pen-peptide是一个有潜在临床应用价值的正电子肽类细胞凋亡显像剂。18F-Pen-peptide was synthesized automatically in a PET-MF-IT-1 module using ＂click chemistry＂. 18F-fluoropentyne was synthesized in reactor No.1 and distilled into reactor No.2, which was pre-loaded with peptide-N3, sodium ascorbate, and CuSOa/TBTA. After reacting at room temperature, the reaction mixture was purified by semi-HPLC, and the fine product 18F-Pen-peptide was collected by solid extraction. The cell uptake of 18F-Pen-peptide in A549 lung adenocarcinoma cells, which were or were not pre-treated with a chemical drug, was determined. The results showed that the yield of lSF-fluoropentyne was 51% from 18F-fluoride （EOS）. The yield of lsF-Pen-peptide was nearly 99% from 18F-fluoropentyne. The total synthesis yield was （21.0±4.5）% （n=6, EOS）. The radiochemistry purity was over 99%, and the specific activity was 870 GBq/μmol, respectively. It took 70 min for lSF-Pen-peptide starting from 18F-fluoride. After chemotherapy, the A549 cells uptake of 18F-Pen-peptide were （0.86±0.04）%, and the cell apoptosis rate was （10.23±2.43）%. The control A549 cells were （0.06±0.01）%, and the cells apoptosis rate was （1.02±0.31）%. The novel radiotracer lsF-Pen-peptide is a promising candidate for future apoptosis imaging in clinical settings.

关 键 词：自动合成 点击合成 凋亡显像 PET 

分 类 号：R445.6[医药卫生—影像医学与核医学] R817.4[医药卫生—诊断学]