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目的:筛选适合监测低葡萄糖代谢的胃黏液腺癌小鼠模型的n 89Zr标记表皮生长因子受体(EGFR)和人表皮生长因子受体2(HER2)单克隆抗体(简称单抗)分子探针。n 方法:通过细胞爬片和移植瘤肿瘤切片验证MGC803胃癌细胞株的EGFR和HER2表达情况；用n 89Zr标记去铁胺-西妥昔单抗(DFO-Cetuximab)和去铁胺-帕妥珠单抗(DFO-Pertuzumab)，制得分别靶向EGFR和HER2的n 89Zr-DFO-Cetuximab和n 89Zr-DFO-Pertuzumab，测定其放化纯；通过细胞结合实验、阻断实验验证n 89Zr-DFO-Cetuximab和n 89Zr-DFO-Pertuzumab与MGC803的结合力和特异性；将12只MGC803荷瘤裸鼠模型分3组(每组4只)，分别注射n 89Zr-DFO-Cetuximab(7.4 MBq/只，74 μg/只)、n 89Zr-DFO-Pertuzumab(7.4 MBq/只，70 μg/只)和n 18F-脱氧葡萄糖(FDG)(7.4 MBq/只)，于注射后4、24和48 h进行microPET显像(n 18F-FDG显像为注射后1 h)；另取8只荷瘤裸鼠，分为n 89Zr-DFO-Cetuximab组和n 89Zr-DFO-Pertuzumab组(各4只)，于探针注射后48 h进行生物分布研究。采用两独立样本n t检验进行组间生物分布比较。n 结果:肿瘤切片免疫荧光染色示MGC803胃癌细胞株EGFR表达量高于HER2。n 89Zr-DFO-Cetuximab和n 89Zr-DFO-Pertuzumab放化纯均大于95%，比活度分别为100和95 MBq/mg；2种探针在生理盐水和胎牛血清(FBS)中稳定性好，放置72 h放化纯仍高于80%。MicroPET显像示MGC803肿瘤部位n 89Zr-DFO-Cetuximab的摄取高于n 18F-FDG和n 89Zr-DFO-Pertuzumab。生物分布实验示，48 h肿瘤n 89Zr-DFO-Cetuximab摄取[每克组织百分注射剂量率(%ID/g)]为56.3±12.0，高于n 89Zr-DFO-Pertuzumab摄取(22.0±3.6；n t＝4.31, n P<0.05)。n 结论:相较于n 89Zr-DFO-Pertuzumab，n 89Zr-DFO-Cetuximab具有更好的无创监测低葡萄糖代谢胃黏液腺癌的潜能。n “,”Objective:To screen n 89Zr-labeled anti-epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) monoclonal antibody molecular probes suitable for monitoring the gastric mucinous adenocarcinoma bearing mouse models with low glucose metabolism.n Methods:The expression of EGFR and HER2 in the MGC803 gastric cancer cell line was verified by analyzing cell slides and xenograft tumor sections. n 89Zr-Deferoxamine (DFO)-Cetuximab and n 89Zr-DFO-Pertuzumab were prepared and the radiochemical purity was detected. Cell binding experiments and blocking experiments were performed to verify the binding ability and specificity of the probes. Twelve gastric mucinous adenocarcinoma bearing mouse models were divided into 3 groups (n n=4 in each group): n 89Zr-DFO-Cetuximab group (7.4 MBq/mouse, 74 μg/mouse), n 89Zr-DFO-Pertuzumab group (7.4 MBq/mouse, 70 μg/mouse) and n 18F-fluorodeoxyglucose (FDG) group (7.4 MBq/mouse). MicroPET imaging was performed at 4, 24 and 48 h (n 18F-FDG group underwent imaging at 1 h only) post-injection. The biodistribution study of n 89Zr-DFO-Cetuximab and n 89Zr-DFO-Pertuzumab was conducted in 2 groups (n n=4 in each group) 48 h after the injection. The independent sample n t test was used for data analysis.n Results:The immunofluorescent staining demonstrated EGFR expression was significantly higher than HER2 expression in MGC803 gastric cancer cell line. The radiochemical purity of n 89Zr-DFO-Cetuximab and n 89Zr-DFO-Pertuzumab were both more than 95%, and the specific activities were 100 and 95 MBq/mg, respectively. The two probes had good stability in normal saline and fetal bovine serum, with the radiochemical purity higher than 80% at 72 h. MicroPET imaging showed that the uptake of n 89Zr-DFO-Cetuximab in the MGC803 tumor was significantly higher than that of n 18F-FDG and n 89Zr-DFO-Pertuzumab. The biodistribution study demonstrated the n 89Zr-DFO-Cetuximab uptake (percentage activity of injection dose per gram of tissue, %ID/g) of tumors at 48 h was significantly higher than that of n 89Zr-DFO-Pertuzumab (56.3±12.0 n vs 22.0±3.6; n t=4.31, n P<0.05).n Conclusion:Compared with n 89Zr-DFO-Pertuzumab, n 89Zr-DFO-Cetuximab has a better potential for non-invasive monitoring of gastric mucinous adenocarcinoma with low glucose metabolism.n