PO.TB02.01 · 肿瘤生物学
近红外 Claudin-1 抗体可准确检测小鼠原发性和转移性结直肠肿瘤
Near-Infrared Claudin-1 antibody enables accurate detection of primary and metastatic colorectal tumors in mice
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摘要 Abstract
中文摘要
背景：Claudin-1 是一种紧密连接蛋白，在结直肠癌（CRC）中经常过表达，是抗体介导的近红外（NIR）荧光成像的一个有吸引力的靶点。本研究评估了一种偶联 IRDye800CW 的抗 Claudin-1 抗体，利用生物发光相关性在原位和转移性小鼠模型中检测并验证结直肠肿瘤。
方法：将表达荧光素酶的 LS174T 人结肠癌细胞植入无胸腺裸鼠体内，建立原位（n = 10）和肝脏（n = 9）肿瘤模型。小鼠在成像前 48 小时静脉注射 50 μg 的 Claudin-1-IRDye800CW。使用 Pearl Trilogy 小动物成像系统和配备 800 nm 荧光功能的 Arthrex Synergy Vision 系统进行体内成像。采用平均荧光强度（mFI）计算肿瘤-背景比（TBR）和肿瘤-肝脏比（TLR）。与荧光素酶生物发光进行共配准以确认探针特异性，离体成像验证生物分布。
结果：在原位模型中，Claudin-1-IRDye800CW 实现了 3.92 的平均 TBR，清晰勾勒出肿瘤边界，而亚毫米级腹膜转移灶（< 1 mm）产生了 2.9 的平均 TBR。在肝脏模型中，平均 TLR 为 3.42，证实了相对于周围组织的选择性肿瘤对比。离体分析进一步提高了对比度（TBR = 16.4；TLR = 4.78）。荧光信号始终与荧光素酶活性共定位，证实了靶向特异性。两种成像系统均展示了高分辨率检测能力，Arthrex 临床腹腔镜在临床相关条件下实现了实时术中可视化。
结论：抗 Claudin-1-IRDye800CW 偶联物可在体内选择性且准确地识别原发性和转移性结直肠肿瘤。强烈的肿瘤对比度以及与生物发光的空间一致性验证了其特异性，而与临床腹腔镜平台的兼容性则凸显了 Claudin-1 靶向 NIR 荧光成像在结直肠癌检测和荧光引导手术方面的转化前景。
查看英文原文 English abstract
Background: Claudin-1, a tight-junction protein frequently overexpressed in colorectal cancer (CRC), is an attractive target for antibody-mediated near-infrared (NIR) fluorescence imaging. This study evaluates an anti-Claudin-1 antibody conjugated to IRDye800CW for detecting and validating colorectal tumors using bioluminescence correlation in orthotopic and metastatic mouse models.
Methods: Luciferase-expressing LS174T human colon cancer cells were implanted into athymic nude mice to establish orthotopic (n = 10) and hepatic (n = 9) tumor models. Mice received 50 µg of Claudin-1-IRDye800CW intravenously 48 hours before imaging. In vivo imaging was performed using both the Pearl Trilogy Small Animal Imaging System and the Arthrex Synergy Vision System equipped for 800 nm fluorescence. Mean fluorescence intensity (mFI) was used to calculate tumor-to-background (TBR) and tumor-to-liver (TLR) ratios. Co-registration with luciferase bioluminescence was used to confirm probe specificity, and ex vivo imaging validated biodistribution.
Results: In the orthotopic model, Claudin-1-IRDye800CW achieved a mean TBR of 3.92, clearly delineating tumor margins, while sub-millimeter peritoneal metastases (< 1 mm) produced a mean TBR of 2.9. In the hepatic model, the mean TLR was 3.42, confirming selective tumor contrast over surrounding tissue. Ex vivo analysis further increased contrast (TBR = 16.4; TLR = 4.78). Fluorescent signals consistently co-localized with luciferase activity, confirming targeting specificity. Both imaging systems demonstrated high-resolution detection, and the Arthrex clinical laparoscope enabled real-time intraoperative visualization under clinically relevant conditions.
Conclusion: The anti-Claudin-1-IRDye800CW conjugate selectively and accurately identifies both primary and metastatic colorectal tumors in vivo. Strong tumor contrast and spatial concordance with bioluminescence validate its specificity, while compatibility with a clinical laparoscopic platform underscores the translational promise of Claudin-1-targeted NIR fluorescence imaging for colorectal cancer detection and fluorescence-guided surgery.
利益披露 Disclosure
J. Bravo, None..
S. Liu, None..
S. Amirfakhri, None..
B. Eddins, None..
K. Kobayashi, None..
J. Zaker, None.
R. Hoffman,
AntiCancer Inc. Employment.
P. Dhawan, None.