Correlation between meta(tetrahydroxyphenyl)chlorin (m-THPC) biodistribution and photodynamic effects in mice.
Analysis of sensitizer kinetics is essential for the performance of light irradiation when tumour concentration and tumour-to-normal tissue ratios are optimal. In this study nude mice were grafted with human adenocarcinoma 15 days before meta(tetrahydroxyphenyl)chlorin (m-THPC) intra-peritoneal (IP) injection. Fluorescence was recorded through an optic fibre spectrofluorometer at 650 (the most intense) and 714 nm, with intensity being proportional to injected dose. In tumour, skin and muscle the maximum fluorescence was obtained with 1.6 mg kg-1 72 h after injection (44 counts per second). Tumour-to-skin and tumour-to-muscle ratios obtained by high performance liquid chromatography (HPLC) analysis and spectrofluorometric measurements decreased between 12 and 72 h (from 15 to 1.5), indicating that tumour selectivity decreases with time. This contrast between selectivity and fluorescence levels was also observed with photodynamic therapy (PDT) results, for which no differences were observed when 10 J cm-2 were delivered at 100 or 200 mW. PDT results were better 24 h after drug administration than at 72 h. Tumour growth decrease (-40%) was found when 1.6 mg kg-1 were injected 24 h before irradiation. For other groups a slower increase (12% vs. 23%) was noted in the first few days after PDT. The paradoxal correlation between fluorometric or HPLC measurements and PDT effects suggests that m-THPC localizes differently with time in tumour components.
Morlet
L
L
Photobiologie des Cancers, Faculté de Pharmacie, Nantes, France.
Vonarx-Coinsmann
V
V
Lenz
P
P
Foultier
M T
MT
de Brito
L X
LX
Stewart
C
C
Patrice
T
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007700:Kinetics; D007834:Lasers; D008027:Light; D008297:Male; D008652:Mesoporphyrins / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008819:Mice, Nude; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013997:Time Factors; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin