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Molecular Imaging Reveals Trastuzumab-Induced Epidermal Growth Factor Receptor Downregulation In Vivo
Ma, Teng1,2; Sun, Xianlei1,2; Cui, Liyang1,2; Gao, Liquan1,2; Wu, Yue1,2; Liu, Hao1,2; Zhu, Zhaohui3; Wang, Fan1,2; Liu, Zhaofei1,2
关键词Molecular Imaging Egfr Her2 Immunotherapy Tumor Response
刊名JOURNAL OF NUCLEAR MEDICINE
2014-06-01
DOI10.2967/jnumed.114.137000
55期:6页:1002-1007
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]METASTATIC BREAST-CANCER ; EGFR MONOCLONAL-ANTIBODY ; PET ; THERAPY ; HER2 ; ANTIGEN ; EXPRESSION ; MECHANISM ; PATHWAYS ; TARGETS
英文摘要

Previous in vitro studies demonstrated that treating tumors expressing both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 with trastuzumab resulted in increased EGFR homodimerization and subsequent rapid downregulation of EGFR. We investigated whether molecular imaging using near-infrared fluorescence (NIRF) imaging and PET probes could sensitively detect trastuzumab-induced EGFR downregulation in vivo. Methods: The F(ab′)2 antibody fragment PaniF(ab′)(2) was generated by digesting the anti-EGFR monoclonal antibody panitumumab. PaniF(ab′)(2) was labeled with either a NIRF dye or Ga-68, and optical imaging and small-animal PET imaging of Dye-PaniF(ab′)(2) and Ga-68-PaniF(ab′)(2), respectively, were performed in HT-29 tumor bearing nude mice treated with trastuzumab or untreated control. Results: Longitudinal NIRF imaging studies revealed significantly reduced tumor uptake of Dye-PaniF(ab′)(2) on days 5 and 7 in trastuzumab-treated HT-29 tumors, compared with control. Western blotting confirmed the downregulation of EGFR after treatment with trastuzumab. Small-animal PET on day 5 after trastuzumab treatment also demonstrated decreased Ga-68-PaniF(ab′)(2) uptake in trastuzumab-treated HT-29 tumors. The tumor uptake value of Ga-68-PaniF(ab′)(2) obtained from PET imaging had an excellent linear correlation with the uptake value measured using biodistribution. Conclusion: The downregulation of EGFR induced by trastuzumab treatment could be detected noninvasively using optical and PET imaging. This molecular imaging strategy could provide a dynamic readout of changes in the tumor signaling and may facilitate the noninvasive monitoring of the early tumor response to drug treatment.

语种英语
所属项目编号81222019 ; 81125011 ; 30930030 ; 81000625 ; 81201127 ; 2013CB733802 ; 2011CB707703 ; 2011YQ030114 ; 2012ZX09102301-018 ; 2012BA1C25B03-16 ; 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:000336829900025
Citation statistics
Cited Times:7[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56067
Collection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.Beijing Union Med Coll Hosp, Dept Nucl Med, Beijing, Peoples R China
Recommended Citation
GB/T 7714
Ma, Teng,Sun, Xianlei,Cui, Liyang,et al. Molecular Imaging Reveals Trastuzumab-Induced Epidermal Growth Factor Receptor Downregulation In Vivo[J]. JOURNAL OF NUCLEAR MEDICINE,2014,55(6):1002-1007.
APA Ma, Teng.,Sun, Xianlei.,Cui, Liyang.,Gao, Liquan.,Wu, Yue.,...&Liu, Zhaofei.(2014).Molecular Imaging Reveals Trastuzumab-Induced Epidermal Growth Factor Receptor Downregulation In Vivo.JOURNAL OF NUCLEAR MEDICINE,55(6),1002-1007.
MLA Ma, Teng,et al."Molecular Imaging Reveals Trastuzumab-Induced Epidermal Growth Factor Receptor Downregulation In Vivo".JOURNAL OF NUCLEAR MEDICINE 55.6(2014):1002-1007.
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