Evaluation of photodynamic therapy-induced heating of hamster melanoma and its effect on local tumour eradication

Abstract

To investigate the contribution of hyperthermia on local tumour eradication by photodynamic therapy (PDT) we quantified PDT induced tumour heating and evaluated its biological effect in vivo. Syrian Golden hamsters bearing an amelanotic melanoma implanted into the dorsal skin received intravenous injections of Photofrin (5 mg kg^-1). Twenty-four hours later tumours were illuminated by red light (630 nm; total energy: 100 J cm^-2) at 100 and 200 mW cm^-2 and tumour surface and tumour centre temperature were measured. The tumoricidally threshold temperature of 43°C was exceeded at 200 mW cm^-2 only, revealing a calculated equivalent treatment time at 43°C of about 10 min. Melanomas treated by PDT at both light intensities disappeared within 48 h and did not reappear locally within the observation period of 32 days. Tumours treated by hyperthermia (water bath) at the maximum temperatures measured during illumination at 200 mW cm^-2 (45·5°C for 500 s) or animals receiving laser light at 200 mW cm^-2 alone showed a significant growth delay compared to controls (p<0·05), whereas illumination at 100 mW cm^-2 alone or hyperthermia corresponding to the maximum temperature obtained at 100 mW cm^-2 (39·5°C for 1000 s) did not alter tumour growth. These data indicate that tumour temperature increased during PDT and exceeded the hyperthermic threshold temperature of 43°C at 200 mW cm^-2. In our tumour model hyperthermia was not necessary for a complete tumour eradication by PDT. Although a combination of PDT and hyperthermia might act in an additive or synergistic manner, an unrecognized overlap of both effects might complicate the interpretation of studies on the mechanisms of PDT.