In vivo anti-tumor activity of photodynamic therapy with intravenous administration of acridine orange, followed by illumination with high-power flash wave light in a mouse osteosarcoma model

Abstract

In a recent study, we demonstrated that a high-power flash wave light (FWL) from a xenon lamp exerted a stronger cytocidal effect against a mouse osteosarcoma cell line than continuous wave light (CWL) in photodynamic therapy with acridine orange (AO-PDT). Based on our in vitro results, we investigated the in vivo anti-tumor activity of AO-PDT using flash wave light from a xenon lamp in a mouse osteosarcoma model. Mouse osteosarcoma cells (LM8) were injected into the subcutaneous tissue of the back of C3H mice, and tumors that grew to approximately 3 mm in diameter were treated by AO-PDT using FWL. AO was administered by intravenous injection and 2 h later the entire body of the mouse was illuminated with FWL from a xenon lamp. Significant growth inhibition of the tumor xenografts was observed as compared with that in the control group, suggesting that AO-PDT with FWL may be useful in the treatment of osteosarcoma. An immunohistochemical study of the tumors treated by AO-PDT showed that the underlying mechanism of the tumor growth inhibition involved both apoptosis and necrosis. In conclusion, it appears that following the intravenous administration of AO, AO-PDT in combination with FWL exerts strong anti-tumor activity. Inhibitory effects against growth of the primary tumor in human patients with osteosarcoma as well as other musculoskeletal sarcomas were also observed.