Colorectal cancer (CRC) continues to be a major health issue even though screening methods have facilitated early detection. Despite the high sensitivity of white-light colonoscopy, it frequently overlooks invasive flat or depressed lesions, which can lead to the development of larger, advanced tumors. Fluorescence molecular imaging (FMI) offers a promising approach for early tumor detection by targeting specific molecular characteristics of lesions. CD24 is upregulated during the adenoma-to-CRC transition, providing a potential target for FMI. Here, we developed a second near-infrared window (NIR-II) fluorescent probe with a high affinity for CD24 and evaluated its efficacy and targeting ability in cellular models, murine models, and clinical samples of CRC. CD24 expression was elevated in 76% of adenomas and 80% of CRCs. In a colitis-associated cancer mouse model, NIR-II imaging with the CD24-targeted probe achieved a significantly higher tumor-to-background ratio compared to conventional NIR-I imaging. The probe demonstrated exceptional sensitivity (92%) and specificity (92%) for detecting CRC, including small lesions less than 1 mm in size. This led to the identification of precancerous lesions missed by white-light detection and lesions missed by NIR-I imaging. Moreover, ex vivo human tissue incubation with the probe supported the potential for intraprocedural lesion identification via topical probe application during colonoscopy. In conclusion, this study successfully demonstrates the potential of CD24-targeted NIR-II imaging for identifying colorectal neoplasia, highlighting its significance for early CRC detection in the gastrointestinal tract.

中文翻译：

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CD24 靶向 NIR-II 荧光成像能够早期检测结直肠肿瘤


尽管筛查方法有助于早期发现，但结直肠癌 (CRC) 仍然是一个主要的健康问题。尽管白光结肠镜检查的灵敏度很高，但它经常忽视侵袭性平坦或凹陷的病变，这可能导致更大、晚期肿瘤的发展。荧光分子成像（FMI）通过针对病变的特定分子特征，为早期肿瘤检测提供了一种有前途的方法。 CD24 在腺瘤向 CRC 转变过程中上调，为 FMI 提供了潜在靶点。在这里，我们开发了第二种对 CD24 有高亲和力的近红外窗口 (NIR-II) 荧光探针，并评估了其在 CRC 细胞模型、小鼠模型和临床样本中的功效和靶向能力。 CD24 表达在 76% 的腺瘤和 80% 的 CRC 中升高。在结肠炎相关癌症小鼠模型中，与传统 NIR-I 成像相比，使用 CD24 靶向探针进行 NIR-II 成像实现了显着更高的肿瘤与背景比。该探针在检测 CRC（包括尺寸小于 1 毫米的小病变）方面表现出卓越的灵敏度 (92%) 和特异性 (92%)。这导致了白光检测遗漏的癌前病变和 NIR-I 成像遗漏的病变的识别。此外，体外人体组织与探针的孵育支持了在结肠镜检查期间通过局部探针应用来识别术中病变的潜力。总之，本研究成功证明了 CD24 靶向 NIR-II 成像在识别结直肠肿瘤方面的潜力，强调了其对胃肠道早期 CRC 检测的重要性。