Medical School of Chinese PLA, Beijing, China.
Department of Stomatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, China.
Int J Cancer. 2022 Aug 1;151(3):450-462. doi: 10.1002/ijc.34049. Epub 2022 May 14.
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.
早期检测和完全切除口腔鳞状细胞癌（OSCC）对于提高患者的生存率和预后至关重要。然而，针对 OSCC 检测的特异性靶向成像探针仍然有限。我们的研究旨在合成一种新型近红外荧光（NIRF）探针，用于 OSCC 的精准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。我们通过对 20 例 OSCC 患者样本的免疫组织化学染色，证实了 GLUT1 的高表达和特异性表达。在人 OSCC 细胞系和 OSCC 肿瘤异种移植模型中，进一步验证了 GLUT1 的特异性表达。基于这些发现，我们利用 GLUT1 抑制剂 WZB117 合成了一种新型的 NIRF 成像探针 WZB117-IR820。荧光分子成像数据显示，WZB117-IR820 经静脉注射后可特异性结合原位 OSCC 小鼠模型中的肿瘤区域，并可进一步应用于精准荧光图像引导手术，在原位 CAL27-fLUC 小鼠肿瘤模型中无残留肿瘤。为了进一步在 OSCC 患者中进行临床转化应用，我们通过局部应用 WZB117-IR820 成像探针实现了 OSCC 肿瘤区域的精准描绘，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，它具有在 OSCC 中进行早期检测和荧光图像引导手术的潜在临床应用价值，且无明显毒性。
