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在结肠癌原位小鼠模型中,荧光素酶表达与荧光抗癌胚抗原抗体对肝转移灶靶向作用的精确共定位

Accurate Co-Localization of Luciferase Expression and Fluorescent Anti-CEA Antibody Targeting of Liver Metastases in an Orthotopic Mouse Model of Colon Cancer.

作者信息

Lee Kyung-Ha, Cox Kristin E, Amirfakhri Siamak, Jaiswal Sunidhi, Liu Shanglei, Hosseini Mojgan, Lwin Thinzar M, Yazaki Paul J, Hoffman Robert M, Bouvet Michael

机构信息

Department of Surgery, University of California San Diego, La Jolla, CA 92037, USA.

VA San Diego Healthcare System, La Jolla, CA 92161, USA.

出版信息

Cancers (Basel). 2024 Sep 29;16(19):3341. doi: 10.3390/cancers16193341.

Abstract

BACKGROUND

The present study aimed to validate the accuracy of a tumor-specific antibody to target liver metastases of colorectal cancer.

METHODS

A humanized anti-CEA antibody conjugated to a fluorescent dye (M5A-IR800) was tested for targeting human colorectal cancer liver metastases (CRLMs) expressing luciferase in an orthotopic mouse model. Orthotopic mouse models of CRLMs were established by implanting fragments of a luciferase-expressing human colorectal cancer cell line, LS174T, in the liver of nude mice. Mice received 50 µg M5A-IR800 72 h prior to imaging. To test co-localization, bioluminescence imaging was performed using D-luciferin, which was given via intraperitoneal injection just prior to imaging.

RESULTS

Tumors were able to be visualized non-invasively through the skin with the luciferase-luciferin signal. Intra-abdominal imaging showed accurate labeling of CRLMs with M5A-IR800, which co-localized with the luciferase-luciferin signal.

CONCLUSIONS

The present results validate the accuracy of a tumor-specific anti-CEA antibody in targeting liver metastases of colorectal cancer.

摘要

背景

本研究旨在验证一种肿瘤特异性抗体靶向结直肠癌肝转移灶的准确性。

方法

在原位小鼠模型中,对一种与荧光染料(M5A-IR800)偶联的人源化抗CEA抗体进行测试,以靶向表达荧光素酶的人结直肠癌肝转移灶(CRLMs)。通过将表达荧光素酶的人结直肠癌细胞系LS174T的片段植入裸鼠肝脏来建立CRLMs的原位小鼠模型。在成像前72小时,小鼠接受50μg M5A-IR800。为了测试共定位,在成像前通过腹腔注射给予荧光素底物,使用生物发光成像进行检测。

结果

通过荧光素酶-荧光素底物信号能够无创地透过皮肤观察到肿瘤。腹内成像显示M5A-IR800对CRLMs的标记准确,且与荧光素酶-荧光素底物信号共定位。

结论

目前的结果验证了一种肿瘤特异性抗CEA抗体靶向结直肠癌肝转移灶的准确性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/85ff/11475688/21175cf24cd5/cancers-16-03341-g001.jpg

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