Photosensitizing efficacy of MTHPC-PDT compared to photofrin-PDT in the RIF1 mouse tumour and normal skin.
The new photosensitizer, meso-tetrahydroxyphenylchlorin (mTPHC) was compared with Photofrin in the murine RIF1 tumour and in normal mouse skin. A range of mTHPC or Photofrin doses were given at intervals of 1 hr to 7 days before illumination. mTHPC-PDT resulted in much higher tumour phototoxicity with longer regrowth delays and more cures. The RIF1 tumour could be effectively treated with 30 J cm-1 (interstitial illumination) at 1 day after mTHPC, whereas 4 to 13 times higher light doses 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 1-day illumination interval. Evaluating both tumour and normal skin photosensitization, the largest therapeutic gain factor (TGF) for mTHPC-PDT was achieved with a low drug dose (0.15 mg kg-1) at 1 day before illumination (TGF = 5.6, relative to Photofrin PDT). The duration of cutaneous photosensitivity for mTHPC was shorter than for Photofrin. The light dose required to produce a desquamation response in 50% of the animals increased more than 20-fold over the period 1 to 7 days after high doses of mTHPC, whereas this light dose only increased by a factor of 2 from 1 to 7 days after Photofrin. The large therapeutic gains seen for mTHPC-mediated PDT compared to Photofrin, plus the rapid fading of skin photosensitization, suggest that mTHPC is a potent photosensitizer suitable for clinical testing.
van Geel
I P
IP
Division of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Amsterdam.
Oppelaar
H
H
Oussoren
Y G
YG
van der Valk
M A
MA
Stewart
F A
FA
D000818:Animals; D005260:Female; D017324:Hematoporphyrin Derivative / Q000494:pharmacology / Q000627:therapeutic use*; D008652:Mesoporphyrins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D017319:Photosensitizing Agents; D012867:Skin / Q000187:drug effects
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D017324:Hematoporphyrin Derivative; C072269:temoporfin