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人源化荧光肿瘤相关糖蛋白 72 抗体在原位小鼠模型中选择性标记结肠癌肝转移。

Humanized Fluorescent Tumor-associated Glycoprotein-72 Antibody Selectively Labels Colon-cancer Liver Metastases in Orthotopic Mouse Models.

机构信息

Department of Surgery, University of California San Diego, San Diego, CA, U.S.A.

Moores Cancer Center, University of California San Diego, San Diego, CA, U.S.A.

出版信息

In Vivo. 2020 Sep-Oct;34(5):2303-2307. doi: 10.21873/invivo.12042.

Abstract

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.

摘要

背景/目的:荧光成像是一种提高肝转移术中检测的方法。本研究旨在确定人源化抗 TAG-72 抗体(huCC49)与近红外染料缀合是否能选择性标记结直肠癌肝转移的原位小鼠模型。

材料和方法

人源化抗 TAG-72(huCC49)与 IRDye800CW(huCC49-IR800)缀合。用人结肠癌细胞系 LS174T 建立原位肝转移裸鼠模型(n=5)。3 周后,给予小鼠 huCC49-IR800,并在 48 小时后进行活体成像。计算平均肿瘤与肝脏比值(TLR)。

结果

活体成像显示,在给予 50μg huCC49-IR800 48 小时后,肿瘤边缘清晰,肝脏荧光最小,平均 TLR=7.53(SD±2.76)。

结论

抗 TAG-72 单克隆抗体与 IRDye800 缀合后,可在结直肠癌肝转移的原位裸鼠模型中对结直肠肿瘤进行清晰、明亮的标记。TAG-72 可能是临床结直肠癌肝转移术中成像的一个有用靶点。

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