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Early Assessment of Tumor Response to Gefitinib Treatment by Noninvasive Optical Imaging of Tumor Vascular Endothelial Growth Factor Expression in Animal Models
Liu, Zhaofei1,2; Sun, Xianlei1,2; Liu, Hao1,2; Ma, Teng1,2; Shi, Jiyun1,3; Jia, Bing1,2; Zhao, Huiyun1,3; Wang, Fan1,2
关键词Egfr Angiogenesis Vegf Molecular Imaging Therapy Response
刊名JOURNAL OF NUCLEAR MEDICINE
2014-05-01
DOI10.2967/jnumed.113.133660
55期:5页:818-823
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Radiology, Nuclear Medicine & Medical Imaging
资助者National Natural Science Foundation of China (NSFC) ; "973"projects ; Ministry of Science and Technology of China ; Ministry of Education of China ; Beijing Natural Science Foundation ; Beijing Nova Program ; National Natural Science Foundation of China (NSFC) ; "973"projects ; Ministry of Science and Technology of China ; Ministry of Education of China ; Beijing Natural Science Foundation ; Beijing Nova Program
研究领域[WOS]Radiology, Nuclear Medicine & Medical Imaging
关键词[WOS]CELL LUNG-CANCER ; FACTOR RECEPTOR INHIBITION ; GENE COPY NUMBER ; TYROSINE KINASE ; VEGF EXPRESSION ; EGFR MUTATIONS ; ZD1839 IRESSA ; ANTI-VEGF ; THERAPY ; PET
英文摘要

Epidermal growth factor receptor (EGFR) expression is upregulated in many types of tumors, and the EGFR tyrosine kinase inhibitor gefitinib has high potential as an anticancer drug. However, accumulating clinical evidence has indicated that only a subset of patients benefit from gefitinib treatment. This study aimed to determine whether optical imaging of vascular endothelial growth factor (VEGF) expression can be an early biomarker for tumor response to gefitinib therapy. Methods: A VEGF-targeting fluorescent probe Dye-BevF(ab′)(2) was prepared and tested in vivo. Longitudinal optical imaging studies using Dye-BevF(ab′)(2) were performed in both 22B (gefitinib-resistant) and A549 (gefitinib-responsive) tumor models at different times (days 0, 2, and 5) before and after gefitinib treatment. The imaging results were validated by ex vivo immunofluorescence staining and enzyme-linked immunosorbent assay. Results: Dye-BevF(ab′)(2) exhibited high specificity for VEGF in vivo. There was no significant change in the Dye-BevF(ab′)(2) uptake in gefitinib-treated 22B tumors, compared with the control group. In contrast, the A549 tumor uptake of DyeBevF(ab′)(2) in the gefitinib-treated group was significantly lower on days 2 and 5 than that in the control group and at the baseline. An in vivo gefitinib treatment study confirmed that 22B tumors were gefitinib-resistant, whereas A549 tumors were gefitinib-responsive. Immunofluorescence staining and enzyme-linked immunosorbent assay confirmed that changes in the Dye-BevF(ab′)(2) uptake were correlated with VEGF expression levels in tumors. Conclusion: Optical imaging of VEGF expression with Dye-BevF(ab′)(2) can be used for the early assessment of tumor response to gefitinib therapy. This approach may also be valuable for preclinical high-throughput screening of novel antiangiogenic drugs.

语种英语
所属项目编号81222019 ; 81125011 ; 30930030 ; 81000625 ; 81201127 ; 2013CB733802 ; 2011CB707703 ; 2011YQ030114 ; 2012ZX09102301 ; 2012BAK25B03 ; 31300 ; BMU20110263 ; 7132131 ; 7132123 ; Z121107002512010
资助者National Natural Science Foundation of China (NSFC) ; "973"projects ; Ministry of Science and Technology of China ; Ministry of Education of China ; Beijing Natural Science Foundation ; Beijing Nova Program ; National Natural Science Foundation of China (NSFC) ; "973"projects ; Ministry of Science and Technology of China ; Ministry of Education of China ; Beijing Natural Science Foundation ; Beijing Nova Program
WOS记录号WOS:000335968000030
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54440
专题北京大学医药卫生分析中心
作者单位1.Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Dept Radiat Med, Beijing 100191, Peoples R China
3.Peking Univ, Med & Hlth Analyt Ctr, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Liu, Zhaofei,Sun, Xianlei,Liu, Hao,et al. Early Assessment of Tumor Response to Gefitinib Treatment by Noninvasive Optical Imaging of Tumor Vascular Endothelial Growth Factor Expression in Animal Models[J]. JOURNAL OF NUCLEAR MEDICINE,2014,55(5):818-823.
APA Liu, Zhaofei.,Sun, Xianlei.,Liu, Hao.,Ma, Teng.,Shi, Jiyun.,...&Wang, Fan.(2014).Early Assessment of Tumor Response to Gefitinib Treatment by Noninvasive Optical Imaging of Tumor Vascular Endothelial Growth Factor Expression in Animal Models.JOURNAL OF NUCLEAR MEDICINE,55(5),818-823.
MLA Liu, Zhaofei,et al."Early Assessment of Tumor Response to Gefitinib Treatment by Noninvasive Optical Imaging of Tumor Vascular Endothelial Growth Factor Expression in Animal Models".JOURNAL OF NUCLEAR MEDICINE 55.5(2014):818-823.
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