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Identification of the optimal therapeutic antibody for fluorescent imaging of cutaneous squamous cell carcinoma

机译:皮肤鳞状细胞癌荧光成像最佳治疗抗体的鉴定

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Intraoperative, real-time fluorescence imaging may significantly improve tumor visualization and resection and postoperatively, in pathological assessment. To this end, we sought to determine the optimal FDA approved therapeutic monoclonal antibody for optical imaging of human cutaneous squamous cell carcinoma (cSCC). A nearinfrared (NIR) fluorescent probe (IRDye800) was covalently linked to bevacizumab, panitumumab or tocilizumab and injected systemically into immunodeficient mice bearing either cutaneous tumor cell lines (SCC13) or cutaneous human tumor explants. Tumors were then imaged and resected under fluorescent guidance with the SPY, an FDA-approved intraoperative imaging system, and the Pearl Impulse small animal imaging system. All fluorescently labeled antibodies delineated normal tissue from tumor in SCC13 xenografts based on tumor-to-background (TBR) ratios. The conjugated antibodies produced TBRs of 1.2-2 using SP Y and 1.6-3.6 using Pearl; in comparison, isotype control antibody IgG-IRDye produced TBRs of 1.0 (SPY) and 0.98 (Pearl). Comparison between antibodies revealed them to be roughly equivalent for imaging purposes with both the SPY and Pearl (p = 0.89 SPY, p = 0.99 Pearl; one way ANOVA). Human tumor explants were also imaged and tumor detection was highest with panitumumab-IRDye800 when using the SP Y (TBR 3.0) and Pearl (TBR 4.0). These data suggest that FDA approved antibodies may be clinically used for intraoperative detection of cSCC.
机译:术中实时荧光成像可显着改善肿瘤的可视化和切除,并在术后进行病理学评估。为此,我们寻求确定用于人皮肤鳞状细胞癌(cSCC)光学成像的最佳FDA批准治疗性单克隆抗体。将近红外(NIR)荧光探针(IRDye800)与贝伐单抗,帕尼单抗或托珠单抗共价连接,然后全身注射入带有皮肤肿瘤细胞系(SCC13)或皮肤人肿瘤外植体的免疫缺陷小鼠中。然后在SPY,FDA批准的术中成像系统和Pearl Impulse小动物成像系统的荧光引导下成像并切除肿瘤。所有荧光标记的抗体均根据肿瘤与背景(TBR)的比例在SCC13异种移植物中描绘了肿瘤的正常组织。偶联的抗体使用SP Y产生的TBR为1.2-2,使用Pearl产生的TBR为1.6-3.6。相比之下,同型对照抗体IgG-IRDye产生的TBR分别为1.0(SPY)和0.98(Pearl)。抗体之间的比较表明,对于SPY和Pearl成像,它们在成像方面大致相同(p = 0.89 SPY,p = 0.99 Pearl;一种方差分析)。当使用SP Y(TBR 3.0)和Pearl(TBR 4.0)时,使用panitumumab-IRDye800对人肿瘤外植体进行成像,并且肿瘤检出率最高。这些数据表明,FDA批准的抗体可在临床上用于术中检测cSCC。

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