Determination of endogenous porphyrins and the maximal HpD tumor/normal skin ratio in SKH-1 hairless mice by light induced fluorescence spectroscopy.
The treatment of skin tumors is an application of photochemotherapy (PCT) which involves an initial administration of a photosensitizer (PS) followed by irradiation with a light beam that causes the PS to produce cytotoxic oxygen species within the tumors. As the PS is also present in normal skin, it is necessary to know how it is distributed between the two tissues. In this study, we have used SKH-1 hairless mice bearing papillomas or carcinomas chemically induced. The biodistribution of hematoporphyrin derivative (HpD) and the tissue autofluorescence measurements were studied by light induced fluorescence spectroscopy. The tumor and normal autofluorescence spectra measured on control mice with papillomas or carcinomas had a very similar shape. However, the principal endogenous porphyrin peak at about 630 nm showed a fluorescence signal amplitude 2 (for papilloma) and 1.5 (for carcinoma)-fold higher than the one found for the normal skin. Moreover, the fluorescence intensity of carcinoma spectrum is 1.4-fold lower than the one of papilloma spectrum at 630 nm. The tissue autofluorescence can be used to distinguish tumor from normal skin and benign from malignant tumor. This difference in fluorescence intensity at 630 nm was directly related to the concentration of endogenous porphyrins in the tumor. Fluorescence intensity ratios between tumor and normal skin were measured 4, 8, 24, 48, 72 and 96 hours after intraperitoneal injection of HpD (5 mg/kg body weight). The best tumor/normal skin ratio was 6.2 for HpD and the time required to reach this ratio was 48 h. HpD showed a moderate selectivity since the ratio was higher than 1 during the four first days. Photodynamic therapy with the same dose of HpD used in this biodistribution study must also be carried out to verify that the maximal tumor/skin ratio corresponds to the maximal efficiency of HpD.
Bossu
E
E
Laboratoire d'Hématologie, Physiologie et Biologie Cellulaire, Faculté des Sciences Pharmaceutiques et Biologiques, Université Henri Poincaré-Nancy I, France.
Padilla
J J
JJ
A'Amar
O
O
Parache
R M
RM
Notter
D
D
Vigneron
C
C
Guillemin
F
F
D000818:Animals; D002277:Carcinoma / Q000737:chemistry; D005260:Female; D017324:Hematoporphyrin Derivative / Q000032:analysis* / Q000494:pharmacology*; D051379:Mice; D008812:Mice, Hairless; D010212:Papilloma / Q000737:chemistry; D012867:Skin / Q000737:chemistry*; D012878:Skin Neoplasms / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D014018:Tissue Distribution
D017324:Hematoporphyrin Derivative