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Novel fluorescent GLUT1 inhibitor for precision detection and fluorescence image-guided surgery in oral squamous cell
Yu Tian1,2,3, Chu Tang4, Guangyuan Shi5
1Medical School of Chinese PLA, Beijing, China.
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.
Insights
A new near-infrared fluorescence (NIRF) probe, WZB117-IR820, specifically targets oral squamous cell carcinoma (OSCC) by binding to glucose transporter 1 (GLUT1). This probe enables precise detection and image-guided surgery for improved OSCC patient outcomes.
Area of Science:
- Biomedical imaging
- Molecular diagnostics
- Cancer research
Background:
- Oral squamous cell carcinoma (OSCC) detection and surgical resection are critical for patient survival.
- Limited availability of targeted imaging probes hinders effective OSCC diagnosis and treatment.
- Glucose transporter 1 (GLUT1) is identified as a highly expressed biomarker in OSCC.
Purpose of the Study:
- To synthesize a novel near-infrared fluorescence (NIRF) imaging probe for precise OSCC detection.
- To evaluate the probe's efficacy in fluorescence image-guided surgery for OSCC.
- To assess the probe's potential for clinical translation in OSCC management.
Main Methods:
- Bioinformatics analysis to identify OSCC-specific biomarkers.
- Immunohistochemical staining to validate GLUT1 expression in OSCC patient samples, cell lines, and xenografts.
- Synthesis of a novel NIRF probe (WZB117-IR820) based on a GLUT1 inhibitor.
- In vivo and ex vivo fluorescence imaging in orthotopic OSCC mouse models.
- Histopathological and immunohistochemical validation of probe performance.
Main Results:
- High and specific expression of GLUT1 was confirmed in OSCC.
- The synthesized WZB117-IR820 probe demonstrated specific tumor targeting in an OSCC mouse model.
- The probe facilitated precise fluorescence image-guided surgery, achieving complete tumor resection.
- Topical application of WZB117-IR820 enabled accurate OSCC delineation in a preclinical setting.
- No observable toxicity was noted with the WZB117-IR820 probe.
Conclusions:
- A novel NIRF imaging probe, WZB117-IR820, was successfully synthesized for OSCC.
- WZB117-IR820 shows significant potential for early OSCC detection and image-guided surgery.
- The probe's specificity for GLUT1 and lack of toxicity support its clinical translational application in OSCC management.
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