Photodynamic therapy using pheophorbide-a and Q-switched Nd:YAG laser on implanted human hepatocellular carcinoma

To evaluate whether administration of pheophorbide-a, a new photosensitizer, followed by use of Q-switched Nd:YAG laser produces a photodynamic reaction, we administered pheophorbide-a to female nude mice (BALB/c-nu) that had been implanted with human hepatocellular carcinoma. Intra-tumoral concentrations of pheophorbide-a were measured by high-performance liquid chromatography. 3 hours after peroral administration of 1 mg/kg body weight, the intra-tumoral concentration was too low to reveal photodynamic effects. Peroral administration of 250 mg/kg body weight, intra-peritoneal administration of 5 mg/kg body weight, and intra-tumoral injection of 200 micrograms yielded 0.24 micrograms/g, 0.83 micrograms/g and 3.68-108 micrograms/g tumor concentrations, respectively. All tumors were irradiated interstitially using a Q-switched Nd:YAG laser at 1064 nm. Only tumors that had been intra-tumorally injected had areas of necrosis larger than those in control tumors. The results suggest that the injection of pheophorbide-a followed by interstitial irradiation using a Q-switched Nd:YAG laser does not induce sufficient photodynamic reaction if the intra-tumoral pheophorbide-a concentration is less than 0.83 micrograms/g tumor tissue, and that photodynamic therapy may be useful if the pheophorbide-a tumor concentration is within the range of 0.83-108 micrograms/g.