论文部分内容阅读
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 study the synthetic route and biological evaluation of O- (2- 18 F-fluoroethyl) -L-tyrosine (~ (18) F-FET) by one-step direct nucleophilic fluorination . Methods N-Boc- (O-TsE) -L-Tyr-OMe] The precursors were labeled with ~ (18) F-FET by direct nucleophilic fluoridation and their biological properties were evaluated by in vitro and in vivo stability and pharmacokinetics. Results ~ (18) F-FET synthesis time was about 50 min, the radiochemical yield was 40% (without attenuation correction), radiochemical purity> 97%. The stability in vitro and in vivo was good. After 3 half-lives were placed in PBS, there was no change in radiochemical purity. No metabolites were found in the blood samples of mice within 1 h after injection of 18 F-FET. ~ (18) F-FET in animals in vivo time-plasma concentration curve in line with the two-compartment model, the distribution is relatively short, the elimination phase is very long, suitable for imaging. Conclusion The precursor of this synthetic route is easily available, with short synthesis time and high radiochemical yield. The product has good in vivo behavior.