Dosimetry for 5-aminolevulinic acid induced protoporphyrin IX photodynamic therapy of Barrett's esophagus

Photodynamic therapy (PDT) is used to cause specific tissue destruction, using photochemical reactions that result from light excitation of photosensitizer, which has localized in the target tissue. The process of photosensitizer photobleaching was investigated to redefine the approach to dosimetry, when applied to treatment of Barrett's esophagus.;An animal model of induced Barrett's esophagus was developed on Sprague-Dawley rats. An Esophagojejunostomy technique was used to generate chronic reflux with pancreaticobiliary and gastric secretion in lower esophagus. Rats with esophagojejunostomy surgery were survived through 5 months and were used in our photosensitizer kinetic study. Columnar epithelium was easily observed, characterized as hyperplasia, ulceration, inflammation and dysplasia. Our study demonstrated a feasible technique to induce Barrett's esophagus model in rat.;In order to interpret real-time dosimetry parameters like photosensitizer concentration and light fluence rate, a passively monitoring in vivo fluorescence dosimeter was developed to measure dosimetry parameters during the PDT treatment. Both phantom and animal studies had been carried out to verify system stability and sensitivity.;The photosensitizer, 5-aminolevulinic acid (ALA) induced Protoporphyrin IX (PpIX), pharmacokinetic was investigated by several methods. PpIX concentration in both induced Barrett's esophagus and normal esophagus was investigated and compared. A PpIX accumulation peak was observed at early hour post ALA administration. PpIX distribution heterogeneity was observed in esophagus and variations were found within individual animals.;Photobleaching and its effects on ALA-PpIX PDT of normal rat esophagus were investigated in detail. Applying the real-time dosimeter, PpIX photobleaching kinetics and light fluence rate kinetics were studied. A PpIX photobleaching model was developed to interpret the relation between photobleaching kinetic, rate and tissue singlet oxygen dynamic. The result suggested that PpIX photobleaching kinetic should be considered to improve our dosimetry model accuracy.;Finally, a dosimetry model was re-defined as a function of real-time photosensitizer concentration, light fluence rate and effective irradiation time. PpIX photobleaching kinetic was applied to determine the effective irradiation time. Optimization of individual treatments could become routine to decrease variability in treatment response and should be applied in ongoing clinical trials.