Department of Surgery, University of California San Diego, San Diego, California; Department of Surgery, VA San Diego Healthcare System, San Diego, California; AntiCancer, Inc., San Diego, California; Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Surgery, University of California San Diego, San Diego, California; Department of Surgery, VA San Diego Healthcare System, San Diego, California.
J Surg Res. 2021 Aug;264:327-333. doi: 10.1016/j.jss.2021.02.022. Epub 2021 Apr 10.
It is difficult to distinguish between a tumor and its liver segment with traditional use of indocyanine green (ICG) alone. In the present study, a method was used to limit ICG to the liver segment adjacent to a tumor. A spectrally-distinct fluorescently-labeled tumor-specific antibody against human carcinoembryonic antigen-related cell-adhesion molecules was used to label the metastatic tumor in a patient-derived orthotopic xenograft mouse model to enable color-coded visualization and distinction of a colon-cancer liver metastases and its adjacent liver segment.
Nude mice received surgical orthotopic implantation in the liver of colon-cancer liver metastases derived from two patients. An anti- carcinoembryonic antigen-related cell-adhesion molecules monoclonal antibody (mAb 6G5j) was conjugated to a near-infrared dye IR700DX (6G5j-IR700DX). After three weeks, mice received 6G5j-IR700DX via tail-vein injection 48 hours before surgery. ICG was intravenously injected after ligation of the left or left lateral Glissonean pedicle resulting in labeling of the segment with preserved blood-flow in the liver. Imaging was performed with the Pearl Trilogy and FLARE Imaging Systems.
The metastatic liver tumor had a clear fluorescence signal due to selective tumor targeting by 6G5j-IR700DX, which was imaged on the 700 nm channel. The adjacent liver segment, with preserved blood-flow in the liver, had a clear fluorescence ICG 800 nm signal, while the left or left lateral segment had no fluorescence signal. Overlay of the images showed clear color-coded differentiation between the tumor fluorescing at 700 nm and the adjacent liver segment fluorescing at 800 nm.
Color-coding of a liver tumor and uninvolved liver segment has the potential for improved liver resection.
传统上单独使用吲哚菁绿（ICG）难以区分肿瘤与其所在的肝段。本研究采用一种方法将 ICG 限制在紧邻肿瘤的肝段。使用针对人癌胚抗原相关细胞黏附分子的荧光标记肿瘤特异性抗体，对患者来源的原位异种移植小鼠模型中的转移性肿瘤进行标记，从而实现对结肠癌肝转移及其相邻肝段的彩色可视化和区分。
裸鼠接受结肠癌肝转移来源的肿瘤的肝原位种植手术。将一种抗癌胚抗原相关细胞黏附分子的单克隆抗体（mAb 6G5j）与近红外染料 IR700DX 连接（6G5j-IR700DX）。3 周后，在手术前 48 小时通过尾静脉注射 6G5j-IR700DX。结扎左或左外侧 Glissonean 蒂后静脉注射 ICG，导致血流保留的肝段标记。使用 Pearl Trilogy 和 FLARE 成像系统进行成像。
转移性肝肿瘤由于 6G5j-IR700DX 的选择性肿瘤靶向作用而具有清晰的荧光信号，可在 700nm 通道上成像。血流保留的相邻肝段具有清晰的荧光 ICG 800nm 信号，而左或左外侧段则没有荧光信号。图像叠加显示，肿瘤在 700nm 处发出荧光，相邻肝段在 800nm 处发出荧光，两者之间有明显的彩色编码区分。
肝肿瘤和未受累肝段的彩色编码具有提高肝切除术效果的潜力。
