Near-infrared-conjugated humanized anti-carcinoembryonic antigen antibody targets colon cancer in an orthotopic nude-mouse model.

Near-infrared-conjugated humanized anti-carcinoembryonic antigen antibody targets colon cancer in an orthotopic nude-mouse model.
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DOI:
10.1016/j.jss.2017.05.069
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发表时间:
2017-10
期刊:
The Journal of surgical research
影响因子:
--
通讯作者:
Bouvet M
Bouvet M
中科院分区:
其他
文献类型:
--
作者:
DeLong JC;Murakami T;Yazaki PJ;Hoffman RM;Bouvet M

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The success of a curative surgery for cancer is dependent on the complete removal of all cancer cells. Tumor visualization by the surgeon can be enhanced through fluorescent-antibody targeting. To further develop such technology, we selected humanized anti-carcinoembryonic antigen (CEA) conjugated to a near-infrared (NIR) dye to target orthotopically implanted human colon cancer in nude mice. The HT-29 human colon cancer cell line was grown in culture and subcutaneously injected subcutaneously in mice. After 3 weeks of growth, tumors were resected and cut into 2 mm3 fragments that were sutured to the cecum of 5 additional nude mice for orthotopic implantation. The tumors were allowed to grow for 4 weeks at which point 3 had successful orthotopic tumor growth and were selected for injection of the humanized anti-CEA antibody conjugated to the NIR dye IRDye800CW (anti-CEA-IRDye800CW). The antibody-dye conjugate (75 μg) was administered via tail vein injection. Images were obtained with the Pearl Trilogy Small Animal Imaging System (LI-COR, Lincoln, NE) with both 700 nm and 800 nm channels and evaluated using Image Studio. Laparotomy was performed 24 hours after labeling the tumors. When imaged through the 800 nm channel, the tumors were observed to be strongly labeled with anti-CEA-IRDye800. At 48 hours laparotomy was repeated which again demonstrated strong labeling of the tumors through the 800 nm channel, but with a lower absolute intensity (in relative units), than at 24 hours for each of the 3 mice imaged. Humanized anti-CEA-IRDye800CW can rapidly and effectively label CEA-expressing human colon cancer in an orthotopic nude mouse model. Given the ability of this technology to target and label tumors with great specificity, the anti-CEA-IRDye800CW is currently being developed for clinical use in fluorescence-guided surgery.
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