用于口腔鳞状细胞癌精准检测和荧光影像引导手术的新型荧光 GLUT1 抑制剂,International Journal of Cancer

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用于口腔鳞状细胞癌精准检测和荧光影像引导手术的新型荧光 GLUT1 抑制剂
International Journal of Cancer ( IF 5.7 ) Pub Date : 2022-04-27 , DOI: 10.1002/ijc.34049
Yu Tian _{1,

2,

3} , Chu Tang ₄ , Guangyuan Shi ₅ , Guorong Wang ₆ , Yang Du _{3,

7,

8} , Jie Tian _{3,

7,

8,

9,

10} , Haizhong Zhang ₂

Affiliation

Medical School of Chinese PLA, Beijing, China.
Department of Stomatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China.
CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, China.
School of Information Science and Technology, University of Science and Technology of China, Hefei, China.
Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Beijing Key Laboratory of Molecular Imaging, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine, Beihang University, Beijing, China.
Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, China.

口腔鳞状细胞癌（OSCC）的早期发现和完全切除对于改善患者的生存和预后至关重要。然而，用于 OSCC 检测的特异性靶向成像探针是有限的。我们的研究旨在合成一种新型近红外荧光 (NIRF) 探针，用于 OSCC 的精确检测和荧光图像引导手术。生物信息学数据表明，葡萄糖转运蛋白 1 (GLUT1) 在 OSCC 患者中高度表达。我们在对来自 20 名 OSCC 患者的样本进行免疫组织化学染色后证明了高特异性 GLUT1 表达。GLUT1 的特异性表达在人类 OSCC 细胞系和 OSCC 肿瘤异种移植物中得到了进一步验证。基于这些发现，GLUT1 抑制剂 WZB117 被用于合成新型 NIRF 成像探针 WZB117-IR820。荧光分子成像数据显示，WZB117-IR820静脉注射后可与原位OSCC小鼠模型肿瘤区域特异性结合，可进一步应用于CAL27-fLUC小鼠原位肿瘤无残留肿瘤的精准荧光影像引导手术模型。对于 OSCC 患者的进一步临床转化应用，在局部应用 WZB117-IR820 成像探针后实现了 OSCC 肿瘤区域的精确描绘，并通过组织病理学和免疫组织化学分析进行了验证。总之，我们合成了一种新型荧光成像探针 WZB117-IR820，该探针具有潜在的临床应用，可用于 OSCC 的早期检测和荧光图像引导手术，且无明显毒性。

"点击查看英文标题和摘要"

Novel fluorescent GLUT1 inhibitor for precision detection and fluorescence image-guided surgery in oral squamous cell carcinoma

Early detection and complete resection of oral squamous cell carcinoma (OSCC) are crucial to improving patient survival and prognosis. However, specifically targeted imaging probes for OSCC detection are limited. Our study aimed to synthesize a novel near-infrared fluorescence (NIRF) probe for precision detection and fluorescence image-guided surgery in OSCC. Bioinformatics data indicated that glucose transporter 1 (GLUT1) is highly expressed in patients with OSCC. We demonstrated high and specific GLUT1 expression upon immunohistochemical staining of samples from 20 patients with OSCC. The specific expression of GLUT1 was further validated in both human OSCC cell lines and OSCC tumor xenografts. Based on these findings, the GLUT1 inhibitor WZB117 was utilized to synthesize a novel NIRF imaging probe, WZB117-IR820. The fluorescence molecular imaging data revealed that WZB117-IR820 could specifically bind to the tumor areas in an orthotopic OSCC mouse model after intravenous injection and could be further applied for precision fluorescence image-guided surgery with no residual tumor in the orthotopic CAL27-fLUC mouse tumor model. For further clinical translational application in patients with OSCC, precise delineation of OSCC tumor areas was achieved after topical application of the WZB117-IR820 imaging probe and was validated by histopathological and immunohistochemical analyses. In conclusion, we synthesized a novel fluorescent imaging probe, WZB117-IR820, which has potential clinical applications for early detection and fluorescence image-guided surgery in OSCC with no observable toxicity.

更新日期：2022-04-27

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