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