Samkoe Kimberley S, Sardar Hira S, Bates Brent D, Tselepidakis Niki N, Gunn Jason R, Hoffer-Hawlik Kevin A, Feldwisch Joachim, Pogue Brian W, Paulsen Keith D, Henderson Eric R
Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
Department of Surgery, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
J Surg Oncol. 2019 Jun;119(8):1077-1086. doi: 10.1002/jso.25468. Epub 2019 Apr 4.
Fluorescence-guided surgery using epidermal growth factor receptor (EGFR) targeting has been performed successfully in clinical trials using a variety of fluorescent agents. We investigate ABY-029 (anti-EGFR Affibody molecule labeled with IRDye 800CW) compared with a small-molecule perfusion agent, IRDye 700DX carboxylate, in a panel of soft-tissue sarcomas with varying levels of EGFR expression and vascularization.
Five xenograft soft-tissue sarcoma cell lines were implanted into immunosuppressed mice. ABY-029 and IRDye 700DX were each administered at 4.98 μM. Fluorescence from in vivo and ex vivo (fresh and formalin-fixed) fixed tissues were compared. The performance of three fluorescence imaging systems was assessed for ex vivo tissues.
ABY-029 is retained longer within tumor tissue and achieves higher tumor-to-background ratios both in vivo and ex vivo than IRDye 700DX. ABY-029 fluorescence is less susceptible to formalin fixation than IRDye 700DX, but both agents have disproportional signal loss in a variety of tissues. The Pearl Impulse provides the highest contrast-to-noise ratio, but all systems have individual advantages.
ABY-029 demonstrates promise to assist in wide local excision of soft-tissue sarcomas. Further clinical evaluation of in situ or freshly excised ex vivo tissues using fluorescence imaging systems is warranted.
使用表皮生长因子受体（EGFR）靶向的荧光引导手术已在多项临床试验中使用多种荧光剂成功进行。我们在一组具有不同EGFR表达水平和血管化程度的软组织肉瘤中，将ABY - 029（用IRDye 800CW标记的抗EGFR亲和分子）与小分子灌注剂IRDye 700DX羧酸盐进行比较。
将五种异种移植软组织肉瘤细胞系植入免疫抑制小鼠体内。ABY - 029和IRDye 700DX均以4.98 μM的剂量给药。比较体内和体外（新鲜和福尔马林固定）固定组织的荧光。评估了三种荧光成像系统对体外组织的性能。
与IRDye 700DX相比，ABY - 029在肿瘤组织中保留的时间更长，在体内和体外均实现了更高的肿瘤与背景比值。ABY - 029荧光比IRDye 700DX对福尔马林固定的敏感性更低，但两种试剂在各种组织中均有不成比例的信号损失。Pearl Impulse提供了最高的对比度噪声比，但所有系统都有各自的优势。
ABY - 029显示出有助于软组织肉瘤广泛局部切除的前景。有必要使用荧光成像系统对原位或新鲜切除的体外组织进行进一步的临床评估。
