正电子发射型计算机断层显像剂~(18)F-FEA-Erlotinib与~(11)C-Erlotinib在HCC827荷瘤小鼠中的显像效果对比研究
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摘要
目的通过对比[~18F]氟乙基-埃罗替尼与[~11C]埃罗替尼在HCC827荷瘤鼠中的正电子发射型计算机断层(PET)显像,评价新PET显像剂~18F-FEAErlotinib的应用潜力。方法经一步亲核取代反应制得~18F-FEA-Erlotinib,而~11C-Erlotinib经[~11C]碘代甲烷(~11CH_3I)甲基化反应合成;先由~18F-FEAErlotinib在HCC827荷瘤鼠中进行1 h Micro-PET动态显像,探索其体内生物分布并确定最佳显像时间;然后分别进行~18F-FEA-Erlotinib与~11C-Erlotinib的1h静态显像,并勾画感兴趣区域(ROI),测定每克组织百分注射剂量率(%ID/g),进行半定量分析。结果经动态显像结果确定1 h为最佳显像时间。1 h静态显像中,~18F-FEA-Erlotinib图像中,肿瘤边界清晰,分辨率、对比度高。1 h静态显像半定量研究发现,~18F-FEA-Erlotinib显像中,肿瘤/脑、肿瘤/肺、肿瘤/骨骼、肿瘤/肌肉的比值分别为5.87±1.21,2.97±0.58,3.33±0.60,3.80±0.72;~11C-Erlotinib显像中,肿瘤/脑、肿瘤/肺、肿瘤/骨骼、肿瘤/肌肉的比值分别为5.48±1.45,1.10±0.34,2.63±0.54,2.10±0.63。结论~18F-FEA-Erlotinib显像肿瘤摄取高,靶/非靶比值较~11C-Erlotinib显像更高,显像清晰,具有较好应用潜力。
Objective To evaluate the imaging study of two positron emission computed tomography( PET) tracers of~18 F-fluoroethyl( FEA)-Erlotinib and~11 C-Erlotinib in HCC827 tumor-bearing nude mice.Methods The~18 F-FEA-Erlotinib and~11 C-Erlotinib were synthesized by nucleophile substitution reactions. The dynamic micro-PET/CT imaging of~18 F-FEA-Erlotinib for 1 h was performed in HCC827 tumor-bearing mice to evaluate the in vivo biological distribution and determine the best imaging time. Static scan of~18 F-FEA-Erlotinib and~11 C-Erlotinib were performed after 1 h injection. The regions of interest( ROIs) were sketched and the semi-quantitative analysis was conducted by the percentage activity of injection dose per gram of tissue( % ID/g). Results Dynamic micro-PET/CT imaging analysis revealed that the best static imaging time was 1 h. The resolution and contrast were good and the tumor boundaries were clear in the~18 F-FEA-Erlotinib static images. In the semi-quantitative analysis,the ratios of tumor/brain,tumor/lung,tumor/bone and tumor/muscle ratios were 5. 87 ± 1. 21,2. 97 ± 0. 58,3. 33 ± 0. 60 and 3. 80 ± 0. 72 respectively for~18 F-FEA-Erlotinib. Meanwhile,the ratios of the same tissues were 5. 48 ± 1. 45,1. 10 ± 0. 34,2. 63 ± 0. 54 and 2. 10 ± 0. 63 respectively for~11 C-Erlotinib. The resolution of~18 F-FEA-Erlotinib imaging was better than~11 C-Erlotinib images.Conclusion The uptake of~18 F-FEA-Erlotinib in HCC827 tumor was visual obviously. The image resolution and the target/non-target ratio of~18 F-FEA-Erlotinib was higher than~11 C-Erlotinib.
Objective To evaluate the imaging study of two positron emission computed tomography( PET) tracers of~18 F-fluoroethyl( FEA)-Erlotinib and~11 C-Erlotinib in HCC827 tumor-bearing nude mice.Methods The~18 F-FEA-Erlotinib and~11 C-Erlotinib were synthesized by nucleophile substitution reactions. The dynamic micro-PET/CT imaging of~18 F-FEA-Erlotinib for 1 h was performed in HCC827 tumor-bearing mice to evaluate the in vivo biological distribution and determine the best imaging time. Static scan of~18 F-FEA-Erlotinib and~11 C-Erlotinib were performed after 1 h injection. The regions of interest( ROIs) were sketched and the semi-quantitative analysis was conducted by the percentage activity of injection dose per gram of tissue( % ID/g). Results Dynamic micro-PET/CT imaging analysis revealed that the best static imaging time was 1 h. The resolution and contrast were good and the tumor boundaries were clear in the~18 F-FEA-Erlotinib static images. In the semi-quantitative analysis,the ratios of tumor/brain,tumor/lung,tumor/bone and tumor/muscle ratios were 5. 87 ± 1. 21,2. 97 ± 0. 58,3. 33 ± 0. 60 and 3. 80 ± 0. 72 respectively for~18 F-FEA-Erlotinib. Meanwhile,the ratios of the same tissues were 5. 48 ± 1. 45,1. 10 ± 0. 34,2. 63 ± 0. 54 and 2. 10 ± 0. 63 respectively for~11 C-Erlotinib. The resolution of~18 F-FEA-Erlotinib imaging was better than~11 C-Erlotinib images.Conclusion The uptake of~18 F-FEA-Erlotinib in HCC827 tumor was visual obviously. The image resolution and the target/non-target ratio of~18 F-FEA-Erlotinib was higher than~11 C-Erlotinib.
引文
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[2]MEMON A A,WEBER B,WINTERDAHL M,et al.PET imaging of patients with non-small cell lung cancer employing an EGF receptor targeting drug as tracer[J].Brit J Cancer,2011,105(12):1850-1855.
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[4]WEBER B,WINTERDAHL M,MEMON A A,et al.Erlotinib accumulation in brain metastases from non-small cell lung cancer:visualization by positron emission tomography in a patient harboring a mutation in the epidermal growth factor receptor[J].J Thorac Oncol,2011,6(7):1287-1289.
[5]MEMON A A,JAKOBSEN S,DAGNAES H F,et al.Positron Emission Tomography(PET)imaging with[11C]-labeled erlotinib:a micro-PET study on mice with lung tumor xenografts[J].Cancer Res,2009,69(3):873-879.
[6]ABOURBEH G,ITAMAR B,SALNIKOV O,et al.Identifying erlotinib-sensitive non-small cell lung carcinoma tumors in mice using[11C]erlotinib PET[J].Ejnmmi Res,2015,5(1):4.
[7]PETRULLI J R,SULLIVAN J M,ZHENG M Q,et al.Quantitative analysis of[11C]-erlotinib PET demonstrates specific binding for activating mutations of the EGFR kinase domain[J].Neoplasia,2013,15(12):1347-1353.
[8]MEMON A A,WEBER B,WINTERDAHL M,et al.PET imaging of patients with non-small cell lung cancer employing an EGF receptor targeting drug as tracer[J].Brit J Cancer,2011,105(12):1850-1855.