THE EFFECT OF FLUENCE RATE ON TUMOR AND NORMAL TISSUE RESPONSES TO PHOTODYNAMIC THERAPY

Photodynamic therapy (PDT), carried out at low fluence rates, may enha nce tumor response as well as affect treatment selectivity. We have st udied the effects of fluence rate on the response of the murine radiat ion-induced fibrosarcoma (RIF) to PDT using Photofrin(R) (5 mg/kg), Tu mor response was tested over a large range of fluence rates (10-200 mW /cm(2)) and fluences (25-378 J/ cm(2)), Low fluence rates were more ef ficient; similar to 60 J/cm(2) at 10 mW/cm(2) was needed to achieve th e same tumor growth delay as similar to 100 J/cm(2) at 150 mW/cm(2) an d similar to 150 J/cm(2) at 200 mW/cm(2). Despite this increased effic iency, lower fluence rates still required longer treatment times for e quivalent anti-tumor effects: 95 min for 57 J/cm(2) at 10 mW/cm(2) ver sus 11 min for 100 J/cm(2) at 150 mW/cm(2). Effects of fluence rate on the PDT toxicity to normal tissue were examined through the response of the murine (C3H) foot to Photofrin(R) PDT, Treatment with condition s that produced equivalent tumor responses, i,e, 57 J/cm(2) at 10 mW/c m(2) and 100 J/cm(2) at 150 mW/cm(2), resulted in a more severe foot r esponse at the higher fluence rate (median peak response: 0.9 at 10 mW /cm(2), 1.5 at 150 mW/cm(2)) with more time required for tissue to ret urn to normal (8 days at 10 mW/cm(2), at least 30 days at 150 mW/cm(2) ). However, when feet were treated with an equal fluence of 100 J/cm(2 ) 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 re sponse. If this increased efficiency is accounted for by lowering trea tment fluence, lower fluence rates also may result in a more favorable normal tissue response to treatment.