In-vivo topical mucosal delivery of a fluorescent deoxy-glucose delineates neoplasia from normal in a preclinical model of oral epithelial neoplasia

Metabolic imaging of oral cavity mucosal surfaces could benefit early detection of oral squamous cell carcinoma (OSCC) and oral epithelial dysplasia (OED). Fluorescent deoxy-glucose agents provide contrast for glucose metabolism similar to ¹⁸FDG-PET imaging and allow use of optical imaging, which provides high resolution and lower potential cost. However, in-vivo topical mucosal delivery of fluorescent deoxy-glucose agents without injection or tissue resection has not been shown. We introduce in-vivo optical imaging of neoplasia following mucosal delivery of 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) in an OSCC/OED hamster model and demonstrate uptake into epithelium across the mucosal surface without injection or disrupting the epithelium. 2-NBDG fluorescence intensity following 30-minutes topical application was 6-fold and 4-fold higher in OSCC and OED, respectively, compared to normal mucosa. Receiver operator characteristic analysis show 83% sensitivity and 73% specificity for detection of neoplasia vs benign (normal and inflammation). Faster 2-NBDG fluorescence temporal decay in neoplasia indicated higher uptake and glucose metabolic rate than normal mucosa. Mucosal delivery of 2-NBDG by topical application to the in-vivo oral surface is feasible and delineates neoplasia from normal mucosa, providing in-vivo noninvasive molecular imaging of dysregulated glucose metabolism, which could benefit preclinical studies of carcinogenesis or be developed for use in early detection.