Determination of the maximal carcinoma/normal skin ratio after HpD or m-THPC administration in Hairless mice (SKH-1) by fluorescence spectroscopy.
The two major steps in our study on the treatment of skin carcinomas by photochemotherapy (PCT) were the development of a skin tumor model in Hairless mice by a chemical carcinogenesis and the use of fluorescence spectroscopy, a semi-quantitative and non-invasive method, in order to determine the time after i.p. injection of photosensitizer when the tumor/normal skin ratio was the highest. A three-step carcinogenesis protocol provided mice bearing carcinomas and these were used to determine the tumor/normal skin ratios of two photosensitizers by fluorescence spectroscopy. Hematoporphyrin derivative (HpD) (5 mg/kg body weight) and m-tetra(hydroxyphenyl) chlorine (m-THPC) (0.3 mg/kg body weight) were injected i.p., and fluorescence was measured at 1, 4, 8, 12, 24, 48, 72 and 96 h after injection. The best carcinoma/normal skin ratio would be 3.2+/-1.4 for HpD and 2.7+/-2.1 for m-THPC, respectively. The delays required to reach these ratios were 72 h for HpD and 24 h for m-THPC. These results have to be considered with caution due to the high SEs and they must be confirmed by organic extraction. Photodynamic therapy with the same doses of HpD and m-THPC used in this pharmacokinetic study has to be carried out in order to compare the toxicities of the two photosensitizers and to determine which one is the best for this type of tumor.
Bossu
E
E
Laboratoire d'Hématologie, Physiologie et Biologie Cellulaire, Faculté des Sciences Pharmaceutiques et Biologiques, Université Henri Poincaré-Nancy I, France.
Padilla-Ybarra
J J
JJ
Notter
D
D
Vigneron
C
C
Guillemin
F
F
D000818:Animals; D002277:Carcinoma / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006415:Hematoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D008652:Mesoporphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008812:Mice, Hairless; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011237:Predictive Value of Tests; D012867:Skin / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D014018:Tissue Distribution
D006415:Hematoporphyrins; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin