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Lu-177-Labeled Antibodies for EGFR-Targeted SPECT/CT Imaging and Radioimmunotherapy in a Preclinical Head and Neck Carcinoma Model
Liu, Zhaofei1,2; Ma, Teng1,2; Liu, Hao1,2; Jin, Zhongxia1,2; Sun, Xianlei1,2; Zhao, Huiyun1; Shi, Jiyun1; Jia, Bing1,2; Li, Fang3; Wang, Fan1,2
关键词Epidermal Growth Factor Receptor Antibody Small-animal Imaging Targeted Therapy
刊名MOLECULAR PHARMACEUTICS
2014-03-01
DOI10.1021/mp4005047
11期:3页:800-807
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]GROWTH-FACTOR RECEPTOR ; METASTATIC COLORECTAL-CANCER ; SQUAMOUS-CELL CARCINOMA ; BINDING-SITE BARRIER ; MONOCLONAL-ANTIBODY ; CETUXIMAB THERAPY ; QUANTITATIVE PET ; PANITUMUMAB ; EXPRESSION ; CHEMOTHERAPY
英文摘要

Epidermal growth factor receptor (EGER) has been well characterized as an important target for cancer therapy. Immunotherapy based on EGFR-specific antibodies (e.g., panitumumab and cetuximab) has shown great clinical promise. However, increasing evidence has indicated that only a subgroup of patients receiving these antibodies will benefit from them, and even patients who do initially experience a major response may eventually develop therapeutic resistance. In this study, we investigated whether panitumumab and cetuximab can serve as delivery vehicles for tumor-targeted radionuclide therapy in a preclinical tumor model that did not respond to immunotherapy. The in vitro toxicity and cell binding properties of panitumumab and cetuximab were characterized. Both antibodies were conjugated with 1,4,7,10-tetraazadodecane-N,N′,N ′′,N′′′-tetraacetic acid (DOTA) and radiolabeled with Lu-177. Small-animal SPECT/CT, biodistribution, and radioimmunotherapy (RIT) studies of Lu-177-DOTA-panitumumab (Lu-177-Pan) and Lu-177-DOTA-cetuximab (Lu-177-Cet) were performed in the UM-SCC-22B tumor model. Both Lu-177-Pan and Lu-177-Cet exhibited favorable tumor targeting efficacy. The tumor uptake was 20.92 +/- 4.45, 26.10 +/- 5.18, and 13.27 +/- 1.94% ID/g for Lu-177-Pan, and 15.67 +/- 3.84, 15.72 +/- 3.49, and 7.82 +/- 2.36% ID/g for Lu-177-Cet at 24, 72, and 120 h p.i., respectively. RIT with a single dose of 14.8 MBq of Lu-177-Pan or Lu-177-Cet significantly delayed tumor growth. Lu-177-Pan induced more effective tumor growth inhibition due to a higher tumor uptake. Our results suggest that panitumumab and cetuximab can function as effective carriers for tumor-targeted delivery of radiation, and that RIT is promising for targeted therapy of EGFR-positive tumors, especially for those tumors that are resistant to antibody-based immunotherapy.

语种英语
WOS记录号WOS:000332348600014
项目编号2013CB733802 ; 2011CB707703 ; 81125011 ; 81222019 ; 30930030 ; 81000625 ; 81201127 ; 2011YQ030114 ; 2012ZX09102301-018 ; 2012BAK25B03-16 ; 31300 ; BMU20110263 ; 7132131 ; 7132123 ; Z121107002512010
资助机构"973" projects ; National Natural Science Foundation of China (NSFC) ; Ministry of Science and Technology of China ; Ministry of Education of China ; Beijing Natural Science Foundation ; Beijing Nova Program
引用统计
被引频次:17[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/400002259/57955
专题北京大学医药卫生分析中心
北京大学基础医学院
北京大学口腔医学院_中心实验室
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 100857, Peoples R China
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GB/T 7714
Liu, Zhaofei,Ma, Teng,Liu, Hao,et al. Lu-177-Labeled Antibodies for EGFR-Targeted SPECT/CT Imaging and Radioimmunotherapy in a Preclinical Head and Neck Carcinoma Model[J]. MOLECULAR PHARMACEUTICS,2014,11(3):800-807.
APA Liu, Zhaofei.,Ma, Teng.,Liu, Hao.,Jin, Zhongxia.,Sun, Xianlei.,...&Wang, Fan.(2014).Lu-177-Labeled Antibodies for EGFR-Targeted SPECT/CT Imaging and Radioimmunotherapy in a Preclinical Head and Neck Carcinoma Model.MOLECULAR PHARMACEUTICS,11(3),800-807.
MLA Liu, Zhaofei,et al."Lu-177-Labeled Antibodies for EGFR-Targeted SPECT/CT Imaging and Radioimmunotherapy in a Preclinical Head and Neck Carcinoma Model".MOLECULAR PHARMACEUTICS 11.3(2014):800-807.
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