Photodynamic therapy: Optimal treatment parameters in murine fibrosarcoma

Abstract

We have investigated the efficacy of photodynamic therapy (PDT) by using two preparations of haematoporphyrin derivative (HPD) that demonstrated different biological activities against experimental murine fibrosarcoma RIF-1 in C3H/He mice. We have been able to demonstrate a minimum clonogenic survival rate of 0.25% by using the more active HPD at 20 mg/kg with a 40-h retention time and a total laser light dose of 100 J/cm2. Further, we noted that clonogenic survival rates of 21.6% and 25.0% respectively could be achieved by using the less active HPD (at 20 mg/kg) with a laser light dose of 150 J/cm2, or the more active HPD (at 20 mg/kg) with a laser light dose of 20 J/cm2. In both cases necrosis of the surrounding normal tissue was absent. Necrosis of the normal tissue surrounding the tumour was shown to be associated with high laser energy (100 J/cm2 and higher) in conjunction with a high dose (20 mg/kg) of the more active HPD. A comparison of survival curves as a function of laser energy for the RIF-1 cells following PDT with the two different preparations of HPD showed a difference in the kinetics of cell death. A curve with a shoulder region and aDo (mean lethal dose) of 41 J/cm2 was obtained when the less active HPD was used, whereas PDT using the more active HPD resulted in a curve with no shoulder and aDo of 16 J/cm2.