INFLUENCE OF FRACTIONATION AND FLUENCE RATE IN PHOTODYNAMIC THERAPY WITH PHOTOFRIN OR MTHPC

Various schedules of fractionated photodynamic therapy (PDT), delivere d at two different light fluence rates, were investigated in the RIF1 tumor model in an attempt to minimize the development of hypoxia durin g PDT and thereby improve tumor response relative to single treatments . The photosensitizers Photofrin and meta-tetrahydroxyphenylchlorin (m THPC) were used in combination with either interstitial or superficial illumination. For both methods of illumination, equal volumetric ligh t doses gave similar tumor responses, as measured by tumor regrowth ti mes and number of cures. Fractionation of superficial illumination did not generally improve tumor response compared with a single illuminat ion with the same total light dose. The only fractionated schedules wh ich demonstrated a trend for increased cure were six fractions of supe rficial illumination given with short (1 h) dark periods between illum inations. Using both photosensitizers, an increase in tumor regrowth t ime occurred when tumors were illuminated interstitially with continuo us light at a linear diffuser output of 50 mW compared with 100 mW per cm diffuser length. Discontinuous illumination with alternating light and dark periods of 30 s improved the tumor response further for mTHP C-mediated PDT at a fluence rate of 100 mW cm(-1). No improvement in r esponse was seen by discontinuous interstitial illumination after Phot ofrin-mediated PDT. These results demonstrate that lower fluence rates and/or fractionating the light dose delivered can improve the respons e of the RIF1 tumor to PDT but that the choice of dark intervals betwe en fractions is critical. (C) 1996 by Radiation Research Society