Topical Application of 5-Aminolevulinic Acid Is Sufficient for Photodynamic Therapy on Vocal Folds: Topical PDT on Vocal Folds

OBJECTIVES: To evaluate the feasibility of topical photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) for vocal fold leukoplakia. STUDY DESIGN: Ex vivo and in vivo. METHODS: 5-ALA was applied topically as a 20% solution to ex vivo canine vocal folds. The penetration depth and concentrations of 5-ALA in tissue were quantified using frozen sectioning and fluorescamine derivatization after 5-ALA contact incubation or topical spraying. Then, 5-ALA solution was sprayed on leporine vocal folds once, twice, or given systemically in vivo. Protoporphyrin IX (PPIX) location was visualized using fluorescence microscopy, and PPIX concentrations were measured using a fluorescent quantitative method. Hematoxylin and eosin (H&E) staining was performed to visualize the histological changes of vocal folds after PDT for each group. RESULTS: Topical incubation of 15 minutes with 5-ALA achieved a penetration depth of over 2 mm and similar concentrations within the superficial 500 μm of epithelium, compared with longer incubation times. Topical spraying of 5-ALA produced sufficient concentrations in vocal folds, but the retention time is short. An in vivo leporine model showed that laryngeal spraying of 20% 5-ALA induced similar penetration depth and concentrations of PPIX compared to systemic administration of 5-ALA. Two sprays of 20% 5-ALA solution with an interval of 30 minutes are needed to produce complete exfoliation of vocal fold epithelium. CONCLUSION: Topical PDT with laryngeal spraying of 20% 5-ALA solution achieves sufficient therapeutic effects and is potentially applicable for the treatment of vocal fold leukoplakia. LEVEL OF EVIDENCE: NA Laryngoscope, 129:E80-E86, 2019.