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

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