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Enhancement of ALA‐PDT Damage by IR‐lnduced Hyperthermia on a Colon Carcinoma Model

Abstract— The interaction of photodynamic therapy (PDT) with 5‐aminolevulinic acid (ALA) and hyperthermia is not well understood. In the present study, significant enhancement of tumor damage was observed after simultaneous application of ALA‐PDT and IR‐induced hyperthermia using a broad‐band incoherent light source. One hour after systemic administration of ALA at a dose of 200 mg/kg, subcutaneously transplanted C26 colon carcinoma tumors were irradiated with two bands of the VersaLight® system, red (R, 580–720 nm) and red plus IR (R+IR, 580–720 nm and 1250–1600 nm). Photoirradiation using the R+IR band at different fluence rates and exposures caused mild heating of the tumor to 39–43°C at a 3 mm depth. Electron microscopy after ALA+R, ALA+R+IR and R+IR treatments showed early mitochondrial swelling that was more pronounced in the ALA+R+IR group. Tumor necrosis assessment, using histology and vital staining, revealed an enhancement of tumor necrosis depth in the ALA+R+IR group compared to ALA+R and R+IR. The results showed that subhyperthermic heating to 39–39.5°C in the ALA+R+IR group decreased the threshold light dose required for 100% tumor necrosis from 210 J/cm2 (observed in the ALA+R group) to 140 J/cm2. A tumor growth delay test, based on tumor volume measurement, also revealed significant enhancement of antitumor effect after application of ALA+R+IR compared to ALA+R.