同位素 ›› 2022, Vol. 35 ›› Issue (5): 368-375.DOI: 10.7538/tws.2021.youxian.115

• 放射性药物与标记化合物 • 上一篇    下一篇

68Ga标记成纤维细胞活化蛋白抑制剂的生物分布和胶质瘤模型micro-PET显像

向一立;钟璇;付晶晶;吴文雨;邵国强;王峰;张俊   

  1. 南京中医药大学,江苏 南京210023;泰州市人民医院 核医学科,江苏 泰州225300;南京医科大学附属南京医院、南京市第一医院 核医学科,江苏 南京210006
  • 出版日期:2022-10-20 发布日期:2022-10-20

The Glioma Model micro-PET Imaging and Biodistribution of 68Ga Labeled Fibroblast Activation Protein Inhibitor

XIANG Yili;ZHONG Xuan;FU Jingjing;WU Wenyu;SHAO Guoqiang;WANG Feng;ZHANG Jun   

  1. Nanjing University of Chinese Medicine, Nanjing 210023, China;Department of Nuclear Medicine, Taizhou People’s Hospital, Taizhou 225300, China;Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China
  • Online:2022-10-20 Published:2022-10-20

摘要: 为研究68Ga标记的成纤维细胞活化蛋白抑制剂(68Ga-FAPI-04)在正常小鼠和胶质瘤裸鼠模型体内的生物学分布及micro-PET显像,以DOTA修饰的成纤维活化蛋白抑制剂为前体合成68Ga-FAPI-04。放射性HPLC测定其标记率,考察放化纯度及体外稳定性,通过测定68Ga-FAPI-04脂水分配系数评估其水溶性。将20只ICR小鼠随机分为5组,尾静脉注射3.7 MBq 68Ga-FAPI-04后5、15、30、60、120 min后处死并取出各脏器,称重并测定放射性计数,计算各组织器官的放射性摄取率。建立U87MG胶质瘤荷瘤鼠模型,进行生物分布及micro-PET显像研究。结果表明,68Ga-FAPI-04的标记率为97.38%±1.32%(n=3),放化纯度为100%,体外稳定性好,亲水性强。ICR正常小鼠生物分布实验显示,68Ga-FAPI-04血液清除快,肾脏为主要排泄器官,脑部放射性摄取低。U87MG荷瘤裸鼠生物分布及micro-PET均显示肿瘤部位有较高的放射性摄取率,68Ga-FAPI-04注射后90 min时肿瘤部位放射性摄取率达到(2.50±0.00)%ID/g。注射后30、60、90、120 min时,肿瘤与正常脑的肿瘤本底比(tumor-to-background ratio, TBR)分别为(6.26±0.09)、(5.06±0.02)、(5.54±1.47)、(5.51±0.03)。研究表明,68Ga-FAPI-04制备简易方便、标记率高、体外稳定性好,主要通过肾脏排泄,在胶质肿瘤模型中具有较好的肿瘤靶向性,micro-PET显像清晰,是潜在的脑肿瘤显像剂。

关键词: 成纤维细胞活化蛋白抑制剂, 镓-68, 同位素标记, 脑胶质瘤, 微型正电子发射计算机断层扫描仪

Abstract: To investigate the biodistribution and micro-PET imaging of 68Ga labeled fibroblast activation protein inhibitor (68Ga-FAPI-04) in normal mice and glioma nude mice, 68Ga-FAPI-04 was synthesized using DOTA-modified fibroblast activation protein inhibitor as precursor. The synthesis yield, radiochemical purity and in vitro stability were analyzed by radio-HPLC, and the hydrophilicity of 68Ga-FAPI-04 was evaluated by lipo-hydro partition coefficient. Twenty ICR mice were randomly divided into 5 groups. 3.7 MBq of 68Ga-FAPI-04 was injected by tail vein per mouse, then the mice were killed at 5, 15, 30, 60, 120 min post-injection(pi.). The main organs and tissues were collected and weighed, then the radioactivity was measured, and the uptake of each tissue or organ was calculated. The nude mice bearing U87MG glioma model were established, then the biodistribution study and micro-PET imaging were performed. The results indicate that the synthesis yield of 68Ga-FAPI-04 was (97.38±1.32)% (n=3), the radiochemical purity was 100%,and the in vitro stability and hydrophilicity were good. The biodistribution study of normal-ICR mice showed that 68Ga-FAPI-04 was cleared from blood rapidly and mainly excreted from kidneys, and the radioactivity uptake in brain was low. The biodistribution and micro-PET of U87MG tumor-bearing nude mice showed high radioactivity at the tumor targets. The uptake of 68Ga-FAPI-04 at the tumor targets reached (2.50±0.00)%ID/g at 90 min pi. The tumor-to-background ratios (TBRs) were(6.26±0.09), (5.06±0.02), (5.54±1.47) and (5.51±0.03) at 30, 60, 90 and 120 min pi., respectively. The preliminary studies indicate that 68Ga-FAPI-04 is synthesized easily with high yields, and is stable in vitro. The radiotracer was mainly excreted from kidneys, and targeting tumor targets with clear images in micro-PET of glioma models. Therefore, 68Ga-FAPI-04 might be a potential brain tumor imaging agent.

Key words: fibroblast activation protein inhibitor, 68Ga, isotope labeling, brain glioma, micro-PET