Post-acute response of 9L gliosarcoma to Photofrin™-mediated PDT in athymic nude mice

Abstract

The objective of this study is to measure the chronic responses of 9L glioma and normal brain to photodynamic therapy (PDT). Tumor size, proliferation activity of glioma cells, and vascular endothelial growth factor (VEGF) expression in both the tumor area and the brain adjacent to tumor (BAT) were observed 7 days after clinically relevant doses of PDT treatment. 9L Gliosarcoma cells were implanted into the brain of 20 athymic nude mice. Fifteen mice were injected intraperitoneally with Photofrin™ at a dose of 2 mg/kg on day 6 after tumor implantation and were treated with laser at different optical doses of 40 J/cm² (n = 5), 80 J/cm² (n = 5), and 120 J/cm² (n = 5) at 24 h after Photofrin injection, respectively. The remaining five tumor-bearing mice served as a tumor-only control. All animals were killed 14 days after tumor implantation. Hematoxylin and eosin and immunostaining were performed to assess tumor volume, VEGF expression in the tumor and the BAT, as well as Ki67 expression in the tumor area. The tumor volume of the mice receiving 80 or 120 J/cm² group was significantly smaller than the control group (p < 0.01). VEGF immunoreactivity in the BAT was significantly increased in the 120 J/cm² PDT-treated mice (p < 0.001), compared with the immunoreactivity seen in untreated mice and those receiving Photofrin and lower optical doses. No significant differences were detected in the proliferation of glioma cells and VEGF expression in the tumor area between these groups. These data indicate that PDT can shrink tumor, especially at the high light dose, and that PDT induces expression of VEGF in the BAT, which is associated with tumor recurrence. Therefore, PDT combined with anti-angiogenic agents may be an effective treatment strategy for glioma.