PHOTOSENSITIZING EFFICACY OF MTHPC-PDT COMPARED TO PHOTOFRIN-PDT IN THE RIF1 MOUSE-TUMOR AND NORMAL SKIN

The new photosensitizer, meso-tetrahydroxyphenylchlorin (mTPHC) was co mpared with Photofrin in the murine RIFI tumour and in normal mouse sk in. A range of mTHPC or Photofrin doses were given at intervals of I h r to 7 days before illumination. mTHPC-PDT resulted in much higher tum our phototoxicity with longer regrowth delays and more cures. The RIFI rumour could be effectively treated with 30 J cm(-1) (interstitial il lumination) at I day after mTHPC, whereas 4 to 13 times higher light d oses were required with Photofrin for an equivalent anti-tumour effect . High doses of mTHPC also caused more skin phototoxicity (superficial illumination) than Photofrin for the I-day illumination interval. Eva luating both tumour and normal skin photosensitization, the largest th erapeutic gain factor (TGF) for mTHPC-PDT was achieved with a low drug dose (0.15 mg kg(-1)) at I day before illumination (TGF = 5.6, relati ve to Photofrin PDT). The duration of cutaneous photosensitivity for m THPC was shorter than for Photofrin. The light dose required to produc e a desquamation response in 50% of the animals increased more than 20 -fold over the period I to 7 days after high doses of mTHPC, whereas t his light dose only increased by a factor of 2 from I to 7 days after Photofrin. The large therapeutic gains seen for mTHPC-mediated PDT com pared to Photofrin, plus the rapid fading of skin photosensitization, suggest that mTHPC is a potent photosensitizer suitable for clinical t esting. (C) 1995 Wiley-Liss, Inc.