Lei Jing, Tian Dianfeng, Zhang Bo, Guo Hongrui, Su Huancheng, Wei Jinzheng, Li Shuai, Li Sufen, Liu Chao, Yang Xiaofeng, Zhang Sanyuan
Department of Gynecology First Hospital of Shanxi Medical University Taiyuan Shanxi China.
Department of Coloproctology First Hospital of Shanxi Medical University Taiyuan Shanxi China.
Bioeng Transl Med. 2025 Feb 4;10(3):e10754. doi: 10.1002/btm2.10754. eCollection 2025 May.
The detection and complete eradication of early-stage small tumors during hysteroscopy remains a significant clinical challenge in preserving fertility for young women with endometrial cancer (EC). The purpose of this study is to verify the feasibility of CD47 as an optical molecular imaging (OMI) target for human EC and to achieve precise localization and identification in hysteroscopic surgery. The results demonstrated that CD47 was overexpressed in EC through bioinformatics, immunohistochemistry, and qRT-PCR. In EC cell lines, CD47-targeted near-infrared photoimmunotherapy (NIR-PIT) induced cytotoxicity in a light dose-dependent manner. Laser confocal microscopy revealed that CD47 intervention significantly increased the phagocytic effect of macrophages on EC cells. In the mice model of partial tumor resection mediated by CD47-targeted OMI, compared to group A (immune therapy alone), group C (NIR-PIT treatment) mice showed a reduced tumor recurrence rate after NIR-PIT intervention. However, the difference did not reach statistical significance. We then evaluated the effect of CD47-targeted NIR-PIT maintenance therapy on tumor recurrence in mice. The results indicated that, compared to untreated animals, the tumor growth rate was slower in the NIR-PIT group using CD47-Alexa Fluor 790 (CD47-AF790), allowing for more sustained tumor control. The freshly isolated whole uterus specimens from EC patients were co-incubated with CD47-AF790, and a significantly enhanced contrast of NIR visible images of tumor tissue was observed, demonstrating high sensitivity and specificity (tumor-to-background ratio >5.05). Finally, under fluorescence microscopy, specific fluorescent signals are observed on tumor cells. In conclusion, accurate localization and excision of EC can be accomplished by employing CD47 optical molecular contrast agents with OMI technology. This method shows potential as a viable and promising approach for the precise diagnosis of EC.
对于患有子宫内膜癌（EC）的年轻女性而言，在宫腔镜检查期间检测并彻底根除早期小肿瘤仍是保留生育能力方面一项重大的临床挑战。本研究的目的是验证CD47作为人EC的光学分子成像（OMI）靶点的可行性，并在宫腔镜手术中实现精确的定位和识别。结果表明，通过生物信息学、免疫组织化学和qRT-PCR检测发现CD47在EC中过表达。在EC细胞系中，靶向CD47的近红外光免疫疗法（NIR-PIT）以光剂量依赖性方式诱导细胞毒性。激光共聚焦显微镜显示，CD47干预显著增强了巨噬细胞对EC细胞的吞噬作用。在由靶向CD47的OMI介导的部分肿瘤切除小鼠模型中，与A组（单纯免疫治疗）相比，C组（NIR-PIT治疗）小鼠在NIR-PIT干预后肿瘤复发率降低。然而，差异未达到统计学意义。然后，我们评估了靶向CD47的NIR-PIT维持疗法对小鼠肿瘤复发的影响。结果表明，与未治疗的动物相比，使用CD47- Alexa Fluor 790（CD47-AF790）的NIR-PIT组肿瘤生长速度较慢，从而实现了对肿瘤更持久的控制。将EC患者新鲜分离的全子宫标本与CD47-AF790共同孵育，观察到肿瘤组织的近红外可见图像对比度显著增强，显示出高灵敏度和特异性（肿瘤与背景比值>5.05）。最后，在荧光显微镜下，在肿瘤细胞上观察到特异性荧光信号。总之，采用CD47光学分子造影剂和OMI技术可实现EC的精确定位和切除。该方法显示出作为一种可行且有前景的EC精确诊断方法的潜力。
