Fluorescence spectroscopic detection using 5-amino levulinic acid (ALA) may provide an effective, noninvasive approach for early detection of oral cancer. In the present study, the use of ALA-induced fluorescence ratio (red/orange) to differentiate between normal and gingivitis-affected gingiva is investigated. Five dogs with varying degrees of gingivitis are studied. Based on previous studies, a dose of 25 mg/kg of ALA is administered intravenously to the dogs. Autofluorescence and ALA-induced fluorescence from three sites: normal gingiva, pigmented gingiva, and gingivitis, are detected with a fiber optic probe coupled to an optical multichannel analyzer. Four dogs show higher and earlier ALA-induced fluorescence from the gingivitis site as compared to the unpigmented gingiva. In two dogs, ALA-induced fluorescence peaks are seen 15 min after ALA administration. Statistical analysis using mean separation procedures reveal differences in the fluorescence from the various sites in each dog. Using a fluorescence (ratio) cutoff of 1.5, the sensitivity and specificity are found to be 92 and 80%, respectively, 1 h after administration of ALA. The indications from this study—that the characteristic protoporphyrin IX (PpIX) fluorescence is seen earlier and in higher magnitude in more vascular areas of the oral cavity—has implications for oral cancer diagnosis.
Fluorescence spectroscopic detection and photodynamic therapy may provide an effective approach for early detection and treatment of oral cancer. Thus the development of a safe photosensitizer that could enhance the spectroscopic contrast between normal and neoplastic tissue, while allowing for selective photosensitization and treatment of pre-malignant and malignant lesions in the oral cavity, is highly desired. In this study, the pharmacokinetics and a safety of 5-aminolevulinic acid (ALA) that could induce an endogenous precursor of protoporphyrin IX and heme in the biosynthetic pathway was investigated. Two doses of ALA:25 and 75 mg/kg were administered intravenously to 4 and 3 dogs, respectively. A 'wash-out' period of 1 week between administration of each does was allowed to ensure against PpIX build-up. Using an optical multichannel analyzer, the fluorescence from the oral cavity was recorded at 3 sites: buccal mucosa, gums, and the tongue, and also from a remote site, the skin. A fiber optic probe was used to deliver excitation and collect the emitted fluorescence. Results showed that the ALA-induced fluorescence reached a peak at 2-4 hours, and returned to baseline in 24-31 hours. The dogs were stable during the course of the study, minimal vomiting was noted. In conclusion, the study showed that higher doses result in a higher peak at a later time.It was observed that different tissues have different pharmacokinetic response, the tongue and the gums have the highest peak fluorescence values, followed by the buccal mucosa and skin.