Novel fluorescent GLUT1 inhibitor for precision detection and fluorescence image-guided surgery in oral squamous cell carcinoma
Menée à partir de l'analyse immunohistochimique d'échantillons tumoraux prélevés sur 20 patients atteints d'un carcinome épidermoïde de la cavité buccale puis menée à l'aide de lignées cellulaires et de xénogreffes, cette étude met en évidence l'intérêt d'une nouvelle sonde fluorescente, dérivée d'un inhibiteur du transporteur de glucose GLUT1, pour détecter précocement des lésions cancéreuses ou guider l'intervention chirurgicale
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. This 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 following 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. This article is protected by copyright. All rights reserved.