O-(3-^(18)F-氟代丙基)-L-酪氨酸的合成及其生物分布

SYNTHESIS AND BIODISTRIBUTION OF O-(3-^(18)F-FLUOROPROPYL)-L-TYROSINE

采用两步法合成氨基酸代谢显像剂O (3 18F 氟代丙基) L 酪氨酸(FPT)。首先,18F-与1,3 二对甲苯磺酸丙二酯(TsOCH2CH2CH2OTs)发生亲核氟化取代反应,生成3 18F 1 对甲苯磺酸丙酯(18FCH2CH2CH2OTs);然后,18FCH2CH2CH2OTs与L 酪氨酸二钠反应生成FPT。FPT总合成时间约为70min,未校正总放化产率为25%～30%,放化纯度大于95%。FPT在正常小鼠、肿瘤模型、炎症模型鼠体内的生物分布及荷瘤裸鼠PET显像结果表明:肾、肝、肺、血液等脏器放射性摄取较高,滞留时间较长,脑摄取放射性较低。FPT可被肿瘤细胞高摄取,而被炎症组织低摄取。给药后180min,荷瘤裸鼠PET显像清晰,肿瘤/肝脏放射性比值约为1.3。FPT制备简便,可以区分肿瘤和炎症,可望成为一种肿瘤氨基酸代谢PET显像剂。

O(318Ffluoropropyl)Ltyrosine (FPT) as an amino acid tracer for tumors imaging with positron emission tomography (PET) is prepared by a twostep procedure.Firstly,nucleophilic fluorination reaction of 18Ffluoride with 1,3di(4methylphenylsulfonyloxy)propane (TsOCH2CH2CH2OTs) yields 318F1(4methylphenylsulfonyloxy) propane(TsOCH2CH2CH218F),then 18Ffluoroalkylation of Ltyrosine disodium salt with TsOCH2CH2CH2 18F yields FPT.The overall radiochemical yield with no decay correction is 25%～30%,the whole synthesis time is about 70 min,and the radiochemical purity is above 95%.Biodistribution of FPT in normal mice,carcinomabearing nude mice and inflammatory mice,and PET imaging for nude mice bearing human Hep G2 liver cell carcinoma are performed.High uptake and longer retention of FPT in kidney,liver,lung and blood,and low uptake in brain are found.Also,high uptake of FPT in tumor and low uptake of FPT in inflammatory tissue are observed.FPT PET imaging allows a clear delineation of nude mice bearing carcinoma,and tumorliver ratio about 1.3 after 180 min postinjection is found.FPT is easy to prepare and can be used to differentiate between tumor and inflammatory tissue.It could become seem an amino acid tracer for tumors with PET imaging.