Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Cancer Biol Ther. 2013 Mar;14(3):271-7. doi: 10.4161/cbt.23300. Epub 2013 Jan 8.
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 near-infrared (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 SPY 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 SPY (TBR 3.0) and Pearl (TBR 4.0). These data suggest that FDA approved antibodies may be clinically used for intraoperative detection of cSCC.
术中实时荧光成像是一种有前途的方法，它可以显著提高肿瘤可视化和切除的效果，并且在术后病理评估中也有一定的作用。为此，我们旨在确定最佳的美国食品和药物管理局（FDA）批准的治疗性单克隆抗体，用于光学成像人皮肤鳞状细胞癌（cSCC）。我们将近红外（NIR）荧光探针（IRDye800）与贝伐单抗、帕尼单抗或托珠单抗共价连接，并将其系统地注射到携带皮肤肿瘤细胞系（SCC13）或皮肤人类肿瘤外植体的免疫缺陷小鼠体内。然后，我们使用 FDA 批准的术中成像系统 SPY 和 Pearl Impulse 小动物成像系统，在荧光引导下对肿瘤进行成像和切除。所有荧光标记的抗体都根据肿瘤与背景（TBR）比值，将 SCC13 异种移植瘤中的正常组织与肿瘤区分开来。与 IgG-IRDye 等非靶向抗体相比，这些抗体能够产生 1.2-2 的 TBR（使用 SPY）和 1.6-3.6（使用 Pearl）。与抗体的比较表明，对于 SPY 和 Pearl 成像目的而言，它们大致等效（SPY：p = 0.89，Pearl：p = 0.99；单因素方差分析）。我们还对人类肿瘤外植体进行了成像，并且当使用 SPY（TBR 3.0）和 Pearl（TBR 4.0）时，panitumumab-IRDye800 的肿瘤检测效果最高。这些数据表明，FDA 批准的抗体可用于术中检测 cSCC。
