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头颈部鳞状细胞癌近红外标记西妥昔单抗和帕尼单抗的光学成像的临床前比较。

Preclinical comparison of near-infrared-labeled cetuximab and panitumumab for optical imaging of head and neck squamous cell carcinoma.

机构信息

Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Volker Hall G082, 1670 University Blvd, Birmingham, AL, 35233, USA.

出版信息

Mol Imaging Biol. 2013 Dec;15(6):722-9. doi: 10.1007/s11307-013-0652-9.

Abstract

PURPOSE

Though various targets have been proposed and evaluated, no agent has yet been investigated in a clinical setting for head and neck cancer. The present study aimed to compare two fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibodies for detection of head and neck squamous cell carcinoma (HNSCC).

PROCEDURES

Antigen specificities and in vitro imaging of the fluorescently labeled anti-EGFR antibodies were performed. Next, immunodeficient mice (n = 22) bearing HNSCC (OSC-19 and SCC-1) tongue tumors received systemic injections of cetuximab-IRDye800CW, panitumumab-IRDye800CW, or IgG-IRDye800CW (a nonspecific control). Tumors were imaged and resected using two near-infrared imaging systems, SPY and Pearl. Fluorescent lymph nodes were also identified, and all resected tissues were sent for pathology.

RESULTS

Panitumumab-IRDye800CW and cetuximab-IRDye800CW had specific and high affinity binding for EGFR (K D = 0.12 and 0.31 nM, respectively). Panitumumab-IRDye800CW demonstrated a 2-fold increase in fluorescence intensity compared to cetuximab-IRDye800CW in vitro. In vivo, both fluorescently labeled antibodies produced higher tumor-to-background ratios compared to IgG-IRDye800CW. However, there was no significant difference between the two in either cell line or imaging modality (OSC-19: p = 0.08 SPY, p = 0.48 Pearl; SCC-1: p = 0.77 SPY, p = 0.59 Pearl; paired t tests).

CONCLUSIONS

There was no significant difference between the two fluorescently labeled anti-EGFR monoclonal antibodies in murine models of HNSCC. Both cetuximab and panitumumab can be considered suitable targeting agents for fluorescent intraoperative detection of HNSCC.

摘要

目的

尽管已经提出并评估了各种靶点,但目前还没有一种药物在头颈部癌症的临床环境中进行研究。本研究旨在比较两种荧光标记的抗表皮生长因子受体(EGFR)抗体对头颈部鳞状细胞癌(HNSCC)的检测。

方法

进行了荧光标记抗 EGFR 抗体的抗原特异性和体外成像。接下来,患有 HNSCC(OSC-19 和 SCC-1)舌肿瘤的免疫缺陷小鼠(n=22)接受了西妥昔单抗-IRDye800CW、帕尼单抗-IRDye800CW 或 IgG-IRDye800CW(非特异性对照)的全身注射。使用两种近红外成像系统 SPY 和 Pearl 对肿瘤进行成像和切除。还识别了荧光性淋巴结,并将所有切除的组织送检进行病理学检查。

结果

帕尼单抗-IRDye800CW 和西妥昔单抗-IRDye800CW 对 EGFR 具有特异性和高亲和力(K D分别为 0.12 和 0.31 nM)。与西妥昔单抗-IRDye800CW 相比,帕尼单抗-IRDye800CW 的体外荧光强度增加了 2 倍。在体内,与 IgG-IRDye800CW 相比,两种荧光标记的抗体均产生了更高的肿瘤与背景比。然而,在两种细胞系或成像方式中,两种荧光标记的抗体之间均没有显著差异(OSC-19:p=0.08 SPY,p=0.48 Pearl;SCC-1:p=0.77 SPY,p=0.59 Pearl;配对 t 检验)。

结论

在 HNSCC 的小鼠模型中,两种荧光标记的抗 EGFR 单克隆抗体之间没有显著差异。西妥昔单抗和帕尼单抗均可被认为是 HNSCC 荧光术中检测的合适靶向药物。

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Use of panitumumab-IRDye800 to image cutaneous head and neck cancer in mice.使用 panitumumab-IRDye800 对小鼠头颈部皮肤癌进行成像。
Otolaryngol Head Neck Surg. 2013 Jun;148(6):982-90. doi: 10.1177/0194599813482290. Epub 2013 Mar 22.

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