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

Abstract

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.

Clinical Experience with Autofluorescence Guided Oral Squamous Cell Carcinoma Surgery

“…Optical coherence tomography is another technique for distinguishing between positive and negative surgical margins [76,77] Some publications mention a molecular definition of surgical margins, from protein markers to DNA-based techniques, that can evaluate the margins at the subcellular level and can explain, for example, the local recurrence in optical microscope pFM [78][79][80]. Various monoclonal antibodies and other ligands are already being clinically used or researched in this area, which have the ability to mark the structures of tumor cells in a certain way and make them visible intraoperatively, for example by means of fluorescence [12,13,17,18].…”

“…New effective examination and imaging techniques are being developed that allow the surgeon to better visualize the boundaries of the primary tumor before and during the surgery more precisely [12][13][14][15][16][17][18][19][20][21][22][23][24]. With the help of these techniques, it is possible, among other things, to have a positive impact on margin surveillance.…”

The NXDC-MEN-301 Study on 5-ALA for Meningiomas Surgery: An Innovative Study Design for the Assessing the Benefit of Intra-Operative Fluorescence Imaging

“…Apart from brain tumors, efforts are underway to extend FGR to other organ systems as well, not only using 5-ALA [ 17 , 18 , 19 , 20 ], but also other fluorochromes, and study designs resulting in regulatory approval are being intensely discussed [ 21 ].…”

Progress in the Application of Fluorescent Probes in Oral Tumor Diseases

“…As a novel near-infrared light therapeutic tool, SQ890 NPs-Pep has exhibited great promise for enhancing tumor imaging, diagnosis, and therapy. Tian et al [17] utilized a novel OSCC imaging biomarker, glucose transporter 1 (GLUT1), and synthesized a new near-infrared fluorescence probe, WZB117-IR820, based on this. In a model of in situ tongue squamous cell carcinoma, after intravenous injection of WZB117-IR820, the tumor area exhibited a higher specific fluorescence intensity compared to adjacent muscle tissues, with tumor diameters ranging approximately 1-2 millimeters.…”