IN-VITRO AND IN-VIVO EFFECTS OF PHOTODYNAMIC THERAPY ON MURINE MALIGNANT-MELANOMA

Background: The role of photodynamic therapy (PDT) in the treatment of malignant melanoma is not well defined, nor is it known whether the d ark melanoma cells absorb the light used in PDT. Methods: In vitro stu dies: 2 x 10(5) B16 murine melanoma cells were incubated with aluminum phthalocyanine (AlpcS(4), 2.5 mg/kg) and were then subjected to photo radiation (50, 100 or 200 J/cm(2)). Viability was then assessed. In vi vo studies: Histology: C57/B1 mice received 2 x 10(5) B16 cells subcut aneously and were randomized into study (PDT) and three control groups . AlpcS(4) 2.5 mg/kg was injected intraperitoneally and the mice were exposed to light (100 J/cm(2)). After 24 hours they were sacrificed an d underwent autopsies. Survival: 40 mice were randomized into PDT :40 J/cm(2)) and control groups and were monitored for 50 days. Tumor grow th: 40 mice were randomized into one control and three treatment group s (PDT on day 3, 6, or 12 after injection with B16 cells), and were mo nitored for 50 days. Temperature: Tumor temperatures before and at the ene of PDT were recorded. Results: In vitro studies: PDT caused a dec rease in cell viability to 15.5 +/- 0.7%, 11.5 +/- 2.1%, and 1.5 + 0.7 % (at 50, 100, and 200 J/cm(2), respectively; P < .001). A significant reduction in thymidine incorporation was noted at all energy levels. In vivo studies: Histology: PDT caused massive tumor necrosis. Surviva l: PDT prolonged the survival of mice (41 +/- 13.4 days) compared to c ontrols (15.8 +/- 3.8 days, P < .001). Tumor growth: 31 days after inj ection with B16 cells, the tumor size was 2.6 +/- 0.3 cm in the contro l group and 1.6 +/- 0.2, 0.9 +/- 0.3, and 1.0 +/- 0.4 cm in the PDT gr oups (days 3, 6 and 12, respectively: P < .01), Temperature: PDT incre ased skin temperature to 42.8 degrees C +/- 1.3 degrees C, 45.3 degree s C +/- 3.5 degrees C, and 51.7 degrees C +/- 2.7 degrees C at 40, 60, and 100 J/cm(2), respectively (P < .01). Conclusions: Photodynamic th erapy was found to have significant effects in experimental melanoma i n mice. The role of PDT in human melanoma remains to be studied.