O-(2-^(18)F-氟代乙基)-L-酪氨酸的新合成路线及其生物学评价  

A novel synthetic procedure and biological evaluation of O-(2-^(18)F-fluoroethyl )-L-tyrosine

作　　者：王明伟[1] 尹端沚[1] 李世强[1] 程登峰[1] 李谷才[1] 郑明强[1] 蔡汉成[1] 梁胜[1] 沈华[1] 张炯1201800 汪勇先[1] 

机构地区：[1]中国科学院上海应用物理研究所放射性药物研究中心,201800

出　　处：《中华核医学杂志》2006年第4期238-240,共3页Chinese Journal of Nuclear Medicine

基　　金：中国科学院知识创新工程重大基金(KJCX1-SW-08);国家自然科学基金(30371643)

摘　　要：目的研究 O-(2-^(18)F-氟代乙基)-L-酪氨酸(^(18)F-FET)新的一步直接亲核放射氟化法合成路线及其生物学评价。方法以 N-叔丁氧羰基-(O-(2-对甲苯磺酰乙氧基))-L-酪氨酸甲酯[N-BOC-(O-TsE)-L-Tyr-OMe]为标记前体,采用直接亲核放射氟化法合成 ^(18)F-FET,并用体内外稳定性和药代动力学实验评价其生物学性能。结果 ^(18)F-FET 的合成时间约为50 min,放化产率为40%(未经衰减校正),放化纯>97%。体内外稳定性好,在 PBS 中放置3个半衰期后,放化纯没有变化;注射 ^(18)F-FET后1 h 内小鼠血样示踪没有发现代谢产物。^(18)F-FET 在动物体内的时间-血药浓度曲线符合二室模型,分布相较短,消除相很长,适合显像。结论用该合成路线标记前体易得,合成时间短,放化产率高,产物具有良好的体内行为。Objective To investigate a novel synthetic method and biological evaluation of O-（2-^18F-fluoroethyl）-L-tyrosine （^18F-FET） as metabolic PET tracer for brain tumor imaging. Methods ^18F-FET was synthesized via one-step direct nucleophilic radiofluorination from a easily obtained precursor N-butyloxycar- bonyl-（ O-（2-tosyloxyethyl） ）-L-tyrosine methyl ester. Its biological evaluation was performed by experiments with in vivo and in vitro stability tests and its pharmacokinetics. Results ^18F-FET was prepared within 50 min with good radiochemical yield （40%, decay not corrected） and radiochemical purity （ 〉 97% ）. The radiochemical purity was not changed after incubation with PBS for 3 half-life of ^18F and no metabolites were found within 1 h, and it also demonstrated that this tracer was very stable in vivo and in vitro. The pharmacokinetics was fitted to two-compartment model with short distribution phase and long clearance phase. Conclusions ^18F-FET was prepared via direct nucleophilic radiofluorination starting from an easily obtained precursor with shortened synthetic time and good radiochemical yield. It was possessed of good biological properties for brain tumor PET imaging.

关 键 词：氟放射性同位素 酪氨酸 化学合成 小鼠 药代动力学 

分 类 号：R91[医药卫生—药学]