Kinetics, localization, and mechanism of 5-aminolevulinic acid-induced porphyrin accumulation in normal and Barrett's-like rat esophagus

Background and Objectives: Photodynamic therapy may selectively destroy Bar rett's epithelium in the esophagus. To optimize photosensitizer administrat ion, the kinetics of B-aminolevulinic acid (ALA)-induced porphyrin accumula tion in the normal and Barrett's-like esophagus were studied in the rat. Study Design/Materials and Methods: Animals received 200 mg/ kg ALA intrave nously (n = 21) or orally (n = 21). Six rats served as controls. At t = 1, 2, 3, 4, 6, 12, and 24 hr, porphyrin concentration in the esophagus was mea sured by using chemical extraction, and porphyrin localization was determin ed by laser scanning microscopy (LSM). In addition, in 20 animals, porphobi linogen deaminase, ferrochelatase, and iron concentration were determined. In a second group In = 24), an esophagojejunostomy was performed to induce a Barrett's-like esophagus. After 18 weeks, animals received ALA, and LSM w as performed at t = 1, 2, 3, 4, 6, 8, and 12 hr. Results: Porphyrin accumulation in normal mucosa was 3.5-fold higher than i n muscularis, with a maximum at 3 hr after ALA administration. With LSM, st rong homogeneous fluorescence of the squamous epithelium was shown, with mi nor fluorescence of submucosa and muscularis. In Barrett's-like epithelium, fluorescence was heterogeneous but was also restricted to epithelial cells . There was no difference in fluorescence intensity between Barrett's-like and adjacent squamous epithelium. Porphobilinogen deaminase activity was hi gher and iron concentration was lower in the mucosa than in the muscularis (P < 0.001). Conclusion: ALA-induced porphyrin accumulation selectively occurs in esopha geal mucosa, whether normal or Barrett's-like, compared with the muscularis , with a maximum at 3 hr after ALA administration. Selectivity may be cause d by a different activity of heme-synthetic enzymes or relative iron defici ency in the mucose. Lasers Surg. Med. 24:3-13, 1999. (C) 1999 Wiley-Liss, I nc.