胰腺癌摄取^(68)Ga-FAPI-04的PDX动物模型及临床PET/CT显像研究

Uptake of 68Ga-FAPI-04 in pancreatic cancer-PDX animal model and its clinical PET/CT imaging

目的通过^(68)Ga-成纤维细胞激活蛋白抑制剂(FAPI)-04 PET显像探索胰腺癌对FAPI的摄取,为胰腺癌成纤维细胞激活蛋白(FAP)靶向显像提供依据。方法构建胰腺癌-人源肿瘤异种移植(PDX)荷瘤裸鼠模型(n=8),分别行^(68)Ga-FAPI-04和18F-脱氧葡萄糖(FDG)microPET/CT显像(每组各4只),采用两独立样本t检验比较2种显像剂在肿瘤中的每克组织百分注射剂量率(%ID/g)。对5例胰腺癌患者[男4例、女1例,年龄46~74(63.0±11.9)岁]分别行^(68)Ga-FAPI-04与18F-FDG PET/CT显像,采用配对t检验比较2种显像剂在胰腺癌原发灶的最大标准摄取值(SUVmax)及肝转移灶与正常肝组织的SUVmax比值。结果MicroPET/CT显像示,^(68)Ga-FAPI-04在胰腺癌-PDX荷瘤裸鼠肿瘤组织中各个时间点均有显像,注射后60 min,^(68)Ga-FAPI-04在胰腺癌-PDX荷瘤裸鼠肿瘤组织中的摄取显著高于18F-FDG[(6.58±0.44)和(4.29±0.13)%ID/g;t=4.152,P=0.0089]。5例胰腺癌患者^(68)Ga-FAPI-04在胰腺癌原发灶的SUVmax显著高于18F-FDG(16.82±3.08和5.14±2.20;t=6.893,P=0.0001);^(68)Ga-FAPI-04的胰腺癌肝转移灶与正常肝组织的SUVmax比值也显著高于18F-FDG(4.57±1.47和1.30±0.16;t=3.803,P=0.0191)。结论胰腺癌可高度摄取^(68)Ga-FAPI-04,提示FAP有望作为胰腺癌良好的分子靶点,用于胰腺癌PET/CT显像。

Objective To exploring the uptake of fibroblast activation protein(FAP)inhibitor(FAPI)in pancreatic cancer through ^(68)Ga-FAPI-04 PET/CT imaging,and provide a basis for the FAP-targeted imaging of pancreatic cancer.Methods Pancreatic cancer-patient-derived tumor xenograft(PDX)mouse models(n=8)were developed,then ^(68)Ga-FAPI-04 and 18F-FDG microPET/CT imaging were performed(4 in each group).The differences of percentage activity of injection dose per gram of tissue(%ID/g)of ^(68)Ga-FAPI-04 and 18F-FDG were analyzed by independent-sample t test.^(68)Ga-FAPI-04 and 18F-FDG PET/CT imaging were performed in 5 patients(4 males,1 female,age:46-74(63.0±11.9)years)with pancreatic cancer,and the maximum standardized uptake value(SUVmax)of ^(68)Ga-FAPI-04 and 18F-FDG in primary pancreatic cancer and the SUVmax ratio of liver metastases to liver tissue were compared by paired t test.Results MicroPET/CT imaging showed that ^(68)Ga-FAPI-04 was obviously uptaken at all time points in the tumor of PDX mice.The uptake of ^(68)Ga-FAPI-04 in PDX mice 60 min after injection was significantly higher than that of 18F-FDG((6.58±0.44)and(4.29±0.13)%ID/g;t=4.152,P=0.0089).PET/CT showed that the SUVmax of ^(68)Ga-FAPI-04 in pancreatic cancer was significantly higher than that of 18F-FDG(16.82±3.08 and 5.14±2.20;t=6.893,P=0.0001)and the SUVmax ratio of liver metastases to liver tissue of ^(68)Ga-FAPI-04 was also significantly higher than that of 18F-FDG(4.57±1.47 and 1.30±0.16;t=3.803,P=0.0191).Conclusion ^(68)Ga-FAPI-04 can be highly uptaken in pancreatic cancer,suggesting that FAP can be a potential target for PET/CT imaging of pancreatic cancer.