The Effect of Fluence Rate on Tumor and Normal Tissue Responses to Photodynamic Therapy

Photodynamic therapy (PDT), carried out at low fluence rates, may enhance tumor response as well as affect treatment selectivity. We have studied the effects of fluence rate on the response of the murine radiation-induced fibrosarcoma (RIF) to PDT using Photofrin® (5 mg/kg). Tumor response was tested over a large range of fluence rates (10-200 mW/cm²) and fluences (25-378 J/ cm²). Low fluence rates were more efficient; -60 J/cm2 at 10 mW/cm² was needed to achieve the same tumor growth delay as -100 J/cm² at 150 mW/cm² and -150 J/cm2 at 200 mW/cm². Despite this increased efficiency, lower fluence rates still required longer treatment times for equivalent anti-tumor effects: 95 min for 57 J/cm² at 10 mW/cm²versus 11 min for 100 J/cm² at 150 mW/cm². Effects of fluence rate on the PDT toxicity to normal tissue were examined through the response of the murine (C311) foot to Photofrin® PDT. Treatment with conditions that produced equivalent tumor responses, i.e. 57 J/cm² at 10 mW/cm² and 100 J/cm² at 150 mW/cm², resulted in a more severe foot response at the higher fluence rate (median peak response: 0.9 at 10 mW/cm², 1.5 at 150 mW/cm²) with more time required for tissue to return to normal (8 days at 10 mW/cm², at least 30 days at 150 mW/cm²). However, when feet were treated with an equal fluence of 100 J/cm2 at various fluence rates, longer healing times accompanied the lower fluence rate treatments. Overall, this paper demonstrates that lower PDT fluence rates are associated with increased efficiency of tumor response. If this increased efficiency is accounted for by lowering treatment fluence, lower fluence rates also may result in a more favorable normal tissue response to treatment.