Hyperthermia enhances the antitumor effect of photodynamic therapy with ALA hexyl ester in a squamous cell carcinoma tumor model

SummaryBackgroundPhotodynamic therapy (PDT) using 5-aminolevulinic acid is considered to be ineffective in the treatment of tumors with progression to the deep layer. Therefore, for such tumors, a method is required which can enhance the effectiveness of this therapy. We examined the anti tumor effect of the combination of PDT with 5-aminolevulinic acid hexyl ester (hALA) and hyperthermia (HT) in a squamous cell carcinoma (SCC) tumor model.MethodsA tumor model was prepared by subcutaneously implanting SCC into nude mice, and treated with HT, PDT with hALA (hALA-PDT), or hALA-PDT combined with HT (PDT + HT). The treatment was performed by remodeled near infra-red irradiator which allows the generation of two types of rays for PDT and HT. With HT, the tumor was irradiated for raising the temperature with a light dose of 437.5 J/cm2. With hALA-PDT, the tumor treated with 250 mg/kg hALA was irradiated with a light dose of 50 J/cm2. With PDT + HT, the tumor was treated as for hALA-PDT except that the temperature was raised during irradiation with a light dose of 437.5 J/cm2 (including light dose of 50 J/cm2 for PDT).ResultsThe tumor growth rates on Day 12 were 97.10% in HT, 67.55% in hALA-PDT and 33.90% in PDT + HT, and PDT + HT showed significant inhibitory effects on tumor growth, although the anti-tumoral effects of HT and hALA-PDT were not seen.ConclusionhALA-PDT combined with HT demonstrated a significant inhibitory effect on the tumor growth of squamous cell carcinoma showing a progression in the deep layer. This suggests that this therapy is useful for tumors showing progression to the deep layer, which hALA-PDT alone is generally ineffective in treating.