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; 44J/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.

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In recent years, the effect of ultrasound (US) in combination with porphyrins such as a gallium-porphyrin complex (ATX-70) has been reported in the treatment of experimental cancers. Before clinical application of this method, further studies are needed. The transplanted squamous cell carcinomas (5CC) on C3H/He mice were irradiated by a tunable optical parametric oscillator (OPO) laser light or ultrasound, in the presence of several different photosensitizers. The tumor size and survival of mice after treatment were observed. Furthermore, we compared antitumor effects of combined irradiation of laser light and ultrasound with those of single laser light or ultrasound, in the presence of ATX-70 or a pheoforbide derivative (PH-1126). Besides PH-i 126 and ATX-70, the following sensitizers were tested: Photofrin II (Pf-II), hematoporphyrin oligomer (HpO). 5-aminolevulinic acid (5-ALA) and aluminum phthalocyanine tetrasuiphonate (AIPcS4).In the results, it was good effects of antitumor by the laser light treatment in the case of PH-1126 and AIPcS4, ATX-70, HpO nsd AIPcS4 produced betterantitumor effeets by irradiation with ultrasound. The antitumor effects of combined use of laser fight and ultrasound were stronger than those of single laser light or ultrasound in both cases of PH-i 126 and ATX-70.