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

摘要

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.