Combination Effect of Photodynamic and Sonodynamic Therapy on Experimental Skin Squamous Cell Carcinoma in C3H/HeN Mice

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide‐a derivative PH‐1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX‐70, a commonly used sonosensitizer. Mice were injected with either PH‐1126 or ATX‐70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX‐70) or 36 hr (PH‐1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX‐70; 44 J/cm2 of 650 nm for PH‐1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH‐1126 or ATX‐70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92–98%) (additive effect) as compared to either single treatment (27–77%). The combination using PH‐1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT‐treated mice (>120 days) was significantly greater than that in single treatment groups (77–95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2–3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non‐superficial or nodular tumors.