Photodynamic Therapy (PDT) With a New Photosensitizer (Talaporfin Sodium) and a Semiconductor Laser in the Esophagus: A Preclinical Study

Abstract

Backgrounds: Porfimer Sodium (Photofrin®) is now used for Barrett's esophagus and esophageal cancer as PDT photosensitiser. However, there are problems in Photofrin® PDT in that it requires long-term light shielding (one month or longer) and an interval of 48 hours from drug administration to laser irradiation. Talaporfin Sodium (Laserphyrin®) is a new photosensitizer and Laserphyrin® PDT overcomes these problems. However, in human, its safety and efficacy was evaluated in only lung cancer. Aim: To apply Laserphyrin® PDT to human esophageal diseases, the relationship between the dose of laser irradiation in Laserphyrin PDT and the degree of tissue injury in the canine normal esophagus was investigated. Study design and setting: Preclinical dose escalation study in animal model. Material and Methods: A total of 9 beagle dogs (males, 13 14 months) were used. Administration of dosage of Laserphyrin (20 mg/kg) was fixed at 20 mg/kg body in every dogs. The interval from administration of Laserphyrin to irradiation of semiconductor laser was fixed at 60 minute to achieve the same plasma concentration (20 μg/ml) as in Laserphyrin PDT for human lung cancer. The dose of irradiation energy was escalated by three steps at 25, 50, and 100 J (three dogs each) and a 1-cm2 area at 9 o'clock 5 cm oral to the esophago-gastric junction was irradiated. On the next day and seven days later, the esophagus including the irradiated area was examined by endoscopy and the dogs were autopsied for histological evaluation. Blood test was also examined on the next day and 7 days later, and performed autopsy with histological evaluation. Results: The injured area (mm2) on the 7 days after by Laserphyrin PDT was 52 ± 48, 496 ± 430, and 831 ± 691 mm2 by 25, 50, and 100 J, respectively. In the exposure area, the ulcerations were clearly visible, but there were no apparent perforation or fistula even on the 7 days after irradiation in all animals. In the surrounding mucosa of the exposure area, there was no visible injury damage in the animals of 25 J irradiation, but the injury was extended to around the exposure area by 50 J and 100 J. Histologically, hemorrhage, fibrosis and necrosis were observed in submucosal layer and muscle layer in all animals. However, massive hemorrhage were observed in the serosa and out of serosa in the animals of 50-J. Furthermore, severe fibrosis and severe necrosis were observed in out of serosa in he animals of100J. All animals recovered well, without severe complications. Conclusions: This is the first preclinical report of Laserphyrin PDT to the esophagus. Irradiation energy at 25 J was considered within the safe dose to expect beneficial effect in Laserphyrin PDT for the canine normal esophagus. We recommend that this level was desirable to start clinical study of human esophageal disease.