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学科主题: 公共卫生
题名:
Epidermal Growth Factor Receptor-Targeted Radioimmunotherapy of Human Head and Neck Cancer Xenografts Using Y-90-Labeled Fully Human Antibody Panitumumab
作者: Liu, Zhaofei1; Liu, Yan1; Jia, Bing1; Zhao, Huiyun1; Jin, Xiaona2; Li, Fang2; Chen, Xiaoyuan3; Wang, Fan1
刊名: MOLECULAR CANCER THERAPEUTICS
发表日期: 2010-08-01
DOI: 10.1158/1535-7163.MCT-10-0444
卷: 9, 期:8, 页:2297-2308
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: SQUAMOUS-CELL CARCINOMA ; EGFR MONOCLONAL-ANTIBODY ; COLORECTAL-CANCER ; BREAST-CANCER ; INTEGRIN ALPHA(V)BETA(3) ; MDA-MB-435 CELLS ; PHASE-II ; IN-VITRO ; CETUXIMAB ; THERAPY
英文摘要:

Panitumumab (ABX-EGF or Vectibix), the first fully human monoclonal antibody targeting epidermal growth factor receptor (EGFR), was approved by the Food and Drug Administration for treatment of patients with metastatic colorectal cancer. Here, we report for the first time the radioimmunotherapy (RIT) of EGFR-positive human head and neck cancer in a nude mouse model using pure beta(-) emitter Y-90-labeled panitumumab. Biodistribution and planar gamma-imaging studies were carried out with In-111-DOTA-panitumumab. The RIT efficacy of Y-90-DOTA-panitumumab was evaluated in UM-SCC-22B tumor model. CD31, Ki67, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and H&E staining were done on UM-SCC-22B tumor sections after treatment. The tumor uptake of In-111-DOTA-panitumumab in UM-SCC-22B tumor-bearing nude mice was 26.10 +/- 4.93, 59.11 +/- 7.22, 44.57 +/- 9.80, 40.38 +/- 7.76, and 14.86 +/- 7.23 % injected dose per gram of tissue at 4, 24, 72, 120, and 168 hours after injection, respectively. Immunotherapy with cold panitumumab (four doses of 10 mg/kg) did not cause significant antitumor effect. RIT with a single dose of 100 mu Ci 90Y-DOTA-panitumumab caused significant tumor growth delay and improved the survival in UM-SCC-22B tumor model. A single dose of 200 mu Ci Y-90-DOTA-panitumumab led to almost complete tumor regression (tumor volumes were 34.83 +/- 11.11 mm(3) and 56.02 +/- 39.95 mm(3) on days 0 and 46 after treatment, respectively). Histopathologic analysis of tumors and normal organs further validated the therapeutic efficacy and limited systemic toxicity of Y-90-DOTA-panitumumab. The high tumor uptake and prolonged tumor retention, as well as effective therapy, reveal that Y-90-DOTA-panitumumab may be a promising radioimmunotherapeutic agent to treat EGFR-positive solid tumors. Mol Cancer Ther; 9(8); 2297-308. (C) 2010 AACR.

语种: 英语
所属项目编号: 30870728 ; 20820102035 ; 30930030 ; 30900373 ; 2007AA02Z467 ; 2009ZX09103-733 ; 2009ZX09301-010 ; 2009ZX09103-746
项目资助者: National Natural Science Foundation of China ; "863" project ; Ministry of Science and Technology of China ; NIH, National Institute of Biomedical Imaging and Bioengineering
WOS记录号: WOS:000280734200014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50369
Appears in Collections:北京大学医药卫生分析中心_期刊论文

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作者单位: 1.Beijing Union Med Coll Hosp, Dept Nucl Med, Beijing, Peoples R China
2.Peking Univ, Med Isotopes Res Ctr, Beijing 100191, Peoples R China
3.Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA

Recommended Citation:
Liu, Zhaofei,Liu, Yan,Jia, Bing,et al. Epidermal Growth Factor Receptor-Targeted Radioimmunotherapy of Human Head and Neck Cancer Xenografts Using Y-90-Labeled Fully Human Antibody Panitumumab[J]. MOLECULAR CANCER THERAPEUTICS,2010,9(8):2297-2308.
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