Al18F-NOTA-FAPI-04的自动化合成与体内显像

目的:自动化合成Al¹⁸F-1,4,7-三氮杂环壬烷-1,4,7-三乙酸(NOTA)-成纤维细胞激活蛋白抑制剂(FAPI)-04,并进行体内显像,评估其诊断肿瘤的效能。方法:利用All-in-one型自动合成模块合成Al¹⁸F-NOTA-FAPI-04,并进行质量分析;取3只正常BALB/c小鼠和3只4T1小鼠乳腺癌荷瘤小鼠进行PET/CT显像,观察体内Al¹⁸F-NOTA-FAPI-04分布情况;对1例肝细胞肝癌患者(男,51岁)进行Al¹⁸F-NOTA-FAPI-04和18F-FDG PET/CT显像,评估其对肝癌的诊断效能。结果:自动化合成Al¹⁸F-NOTA-FAPI-04的时间约为35 min,合成产率约为(25.2±1.9)%(衰减校正后,n=3),产品为无色透明溶液,pH值为7.0~7.5,其比活度为(46.11±3.07)GBq/μmol(衰减校正后,n=3),放化纯大于99.0%,室温放置6 h后放化纯仍大于98.0%。小鼠体内显像示Al¹⁸F-NOTA-FAPI-04的生理性摄取主要在胆道系统和膀胱中,且高度浓聚于肿瘤病灶区域;肝细胞肝癌患者PET/CT显像示Al¹⁸F-NOTA-FAPI-04和18F-FDG PET/CT在胸骨旁淋巴结、膈上前组淋巴结、肝门区淋巴结、胰十二指肠韧带区淋巴结、腹主动脉旁淋巴结的靶本比值(TBR)分别为4.1、8.9、5.4、4.8、2.2和1.0、2.8、5.0、2.1、1.1。结论:基于All-in-one型自动合成模块合成Al¹⁸F-NOTA-FAPI-04,合成时间较短、产率高、稳定性好,高度浓聚于病灶区域,其PET图像对比度高,诊断性能优异。

Automatic synthesis and in vivo imaging of Al18F-NOTA-FAPI-04

Objective To automatically synthesize Al18F-1,4,7-triazacyclononane-1,4,7-triacetic acid(NOTA)-fibroblast activation protein inhibitor(FAPI)-04,perform PET/CT imaging in vivo,and evaluate its diagnostic efficacy on tumors.Methods Al18F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography(HPLC)equipped with a radioactive detector.Al18F-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice(n=3)and 4T1 breast cancer models(n=3)to determine its biodistribution.Then Al18F-NOTA-FAPI-04 and¹⁸F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient(male,51 years old).Results The synthesis time of Al18F-NOTA-FAPI-04 was about 35 min,and the radiochemical yield was(25.2±1.9)%(attenuation correction,n=3).The product was colorless transparent solution with pH value of 7.0-7.5,and the specific activity was(46.11±3.07)GBq/μmol(attenuation correction,n=3).The radiochemical purity was above 99.0%and was still above 98.0%at room temperature after 6 h.PET/CT imaging in mice showed that physiological uptake of Al18F-NOTA-FAPI-04 was mainly in biliary system and bladder,and Al18F-NOTA-FAPI-04 highly concentrated in tumor xenografts.PET/CT imaging in the patient showed that Al18F-NOTA-FAPI-04 obtained high tumor background ratio(TBR)values of 4.1,8.9,5.4,4.8,2.2 in parasternal lymph nodes,anterior diaphragmatic lymph nodes,hilar lymph nodes,pancreaticoduodenal ligament lymph nodes,abdominal aortic lymph nodes,respectively,while TBR values were 1.0,2.8,5.0,2.1,1.1 by¹⁸F-FDG.Conclusions Al18F-NOTA-FAPI-04 can be synthesized with short time,high radiochemical yield and good stability using All-in-one module.Al18F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.