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Humanized Fluorescent Tumor-associated Glycoprotein-72 Antibody Selectively Labels Colon-cancer Liver Metastases in Orthotopic Mouse Models
In Vivo ( IF 2.3 ) Pub Date : 2020-01-01 , DOI: 10.21873/invivo.12042
Hannah M Hollandsworth 1, 2, 3 , Hiroto Nishino 1, 4 , Michael Turner 1, 2 , Siamak Amirfakhri 1, 2, 3 , Filemoni Filemoni 1, 2, 3 , Robert M Hoffman 1, 2, 3, 4 , Paul J Yazaki 5 , Michael Bouvet 1, 3, 3
Affiliation  

Background/Aim: Fluorescence imaging has been shown to improve intra-operative detection of liver metastasis. The present study aimed to determine whether humanized anti-TAG-72 antibody (huCC49) conjugated to a near-infrared dye provides selective labeling of colorectal-cancer liver metastasis in orthotopic mouse models. Materials and Methods: Humanized anti-TAG-72 (huCC49) was conjugated to IRDye800CW (huCC49-IR800). Orthotopic liver-metastasis nude-mouse models (n=5) were established with the human colon-cancer LS174T cell-line. Three weeks later, mice were administered huCC49-IR800 and intra-vital imaging was performed 48 h later. The mean tumor-to-liver ratio (TLR) was calculated. Results: Intra-vital imaging demonstrated clear tumor margins with minimal liver fluorescence 48 h after administration of 50 μg huCC49-IR800 with mean TLR=7.53 (SD±2.76). Conclusion: Anti-TAG-72 monoclonal antibody conjugated to IRDye800 provides distinct and bright labeling of colorectal tumors in orthotopic nude-mouse models of liver metastasis. TAG-72 may be a useful target for intra-operative imaging of colorectal cancer liver metastasis in the clinic.

中文翻译:

人源化荧光肿瘤相关糖蛋白 72 抗体选择性标记原位小鼠模型中的结肠癌肝转移

背景/目的:荧光成像已被证明可以改善肝转移的术中检测。本研究旨在确定与近红外染料偶联的人源化抗 TAG-72 抗体 (huCC49) 是否在原位小鼠模型中提供了结直肠癌肝转移的选择性标记。材料和方法:人源化抗 TAG-72 (huCC49) 与 IRDye800CW (huCC49-IR800) 偶联。用人结肠癌 LS174T 细胞系建立原位肝转移裸鼠模型 (n=5)。三周后,给小鼠施用 huCC49-IR800,并在 48 小时后进行活体成像。计算平均肿瘤与肝脏比率 (TLR)。结果:在施用 50 μg huCC49-IR800 且平均 TLR = 7 后 48 小时,活体成像显示清晰的肿瘤边缘和最小的肝脏荧光。53 (SD±2.76)。结论:与 IRDye800 偶联的抗 TAG-72 单克隆抗体在原位肝转移裸鼠模型中提供了清晰而明亮的结直肠肿瘤标记。TAG-72可能是临床结直肠癌肝转移术中成像的有用靶标。
更新日期:2020-01-01
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