Al^(18)F-FAPI-74的合成及初步临床应用

Synthesis and preliminary clinical application of Al^(18)F-FAPI-74

目的自动化合成Al^(18)F-成纤维细胞激活蛋白抑制剂(FAPI)-74, 探讨其临床应用价值。方法通过商业化合成模块CFN-MPS-100自动化合成Al^(18)F-FAPI-74, 测其产率、放化纯和稳定性。取16只正常昆明小鼠用随机抽签法分成4组, 注射Al^(18)F-FAPI-74后分别在10、30、60和90 min对小鼠实施安乐死并测量药物在体内的生物分布。取5只大鼠胰腺外分泌细胞AR42J BALB/c荷瘤裸鼠, 注射Al^(18)F-FAPI-74后行60 min的microPET/CT动态扫描, 观察肿瘤摄取情况。对3名志愿者(男1名, 女2名;年龄37、41、43岁)行Al^(18)F-FAPI-74 PET/CT显像, 评价药物的临床应用价值。结果自动化合成Al^(18)F-FAPI-74的时间约35 min, 合成产率为(21.34±3.86)%(未衰减校正, n=5), 放化纯大于99%, 37 ℃放置6 h后放化纯仍大于96%。正常小鼠的生物分布和荷瘤裸鼠microPET/CT动态扫描显示, 在所有时间点肾脏和膀胱Al^(18)F-FAPI-74摄取均较高, 20 min时肿瘤摄取最高, 60 min时肿瘤与肌肉的靶/本底比值最大(3.16±0.01)。志愿者PET/CT显像示, 心肌有少量摄取, 肝脏、肺等大多数器官为本底摄取;肿瘤持续性高摄取, SUVmax最大为17.08。结论 Al^(18)F-FAPI-74合成简单、产率高、质量稳定、小鼠和志愿者显像效果良好, 是1种符合临床诊断要求的显像剂。

Objective To automatically synthesize Al^(18)F-fibroblast activation protein inhibitor(FAPI)-74,and explore its value of clinical application.Methods Al^(18)F-FAPI-74 was synthesized automatically by the commercial synthesis module CFN-MPS-100,and its yield,radiochemical purity and stability were determined.Sixteen normal Kunming(KM)mice were randomly divided into 4 groups and euthanized at 10,30,60 and 90 min after Al^(18)F-FAPI-74 injection,and the biodistribution was measured.MicroPET/CT dynamic scanning(60 min)was performed in 5 rat pancreatic tumor-bearing BALB/c nude mice to observe the tumor uptake.Al^(18)F-FAPI-74 PET/CT imaging was performed on 3 volunteers(1 male,2 females;age:37,41,43 years)to evaluate the clinical application value of Al^(18)F-FAPI-74.Results The automated synthesis time of Al^(18)F-FAPI-74 was about 35 min,with the synthesis yield of(21.34±3.86)%(without attenuation correction,n=5)and the radiochemical purity more than 99%.The radiochemical purity was still more than 96%after placement at 37℃for 6 h.Biodistribution in normal mice and microPET/CT dynamic scanning in tumor-bearing nude mice showed that consistently high uptake in the kidneys and bladder,and the tumor uptake was the highest at 20 min,and the maximum tumor-to-muscle ratio was 3.16±0.01 at 60 min.PET/CT imaging on volunteers showed that there was a small amount of uptake in myocardium,most organs such as the liver and lung had background uptake,and the maximum SUVmax of persistent high uptake of tumor was 17.08.Conclusions Al^(18)F-FAPI-74 has the advantages of simple synthesis,high yield,stable quality and good imaging performance in mice and volunteers.It is a kind of imaging agent that meets the requirements of clinical diagnosis.