Potentiation of photodynamic therapy by heat: Effect of sequence and time interval between treatments in vivo

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Abstract
Photodynamic therapy (PDT) utilizing hematoporphyrin derivative (Hpd) as photosensitizer and an argon‐dye laser as the light source was used alone and in combination with a localized microwave hyperthermia treatment to treat the SMTF mammary carcinoma in mice. A 30‐min heat treatment at 44.5°C was applied 0–8 hr before or after a standard photodynamic treatment (67.5 or 135 J/cm2, given 24 hr post‐7.5 mg/kg Hpd). Potentiation of PDT by heat was found to be related to the sequence of the treatments and the time interval between them.When 44.5°C for 30 min was applied immediately after a 15‐min PDT treatment, significant potentiation was seen (58% long‐term tumor control vs 3 and 10%, respectively, for PDT and heat alone). This potentiation decreased with increasing time between PDT and heat, with tumor control values decreasing to 36, 20, and 14%, when 2, 4, and 8 hr, respectively, were allowed between treatments. Only additive effects of the independent therapies were found when this heat treatment was applied 0–8 hr before PDT.In other experiments, mice were treated with single or fractionated 30‐min PDT treatments (two 15‐min treatments separated by 0‐,‐2‐, 4‐, or 8‐hr intervals). Decreases in tumor control were seen with increasing time interval; only minor differences in tumor control were seen when 4–8 hr was allowed between treatments compared to a single 15‐min treatment.