Tissue distribution and in vivo photosensitising activity of 13,15-[N-(3-hydroxypropyl)]cycloimide chlorin p6 and 13,15-(N-methoxy)cycloimide chlorin p6 methyl ester
Résumé
Photosensitizers 13,15-[N-(3-hydroxypropyl)]cycloimide chlorin p6 (HPC) and 13,15-(N-methoxy)cycloimide chlorin p6 methyl ester (MMC) absorb at 711 nm and possess high photoinduced cytotoxicity in vitro. Here we report, that photodynamic therapy with HPC and MMC provide considerable antitumor effect in mice bearing subcutaneous P338 lymphoma. The highest antitumor effect was achieved at a dose of 4 lmol/kg when 1.5 h delay between dye injection and light irradiation (drug–light interval) was used. According to the confocal spectral imaging studies of tissue sections this drug–light interval corresponds to a maximum of tumor accumulation of MMC and HPC (tumor to skin accumulation ratio is 8–10). Short (15 min) drug–light interval can be used for efficient vasculature-targeted photodynamic therapy with HPC at a dose of 1 lmol/kg, whereasMMCis ineffective at the short drug–light interval. Relationships between the features of tissue distribution and efficacy of photodynamic therapy at different drug–light intervals are discussed for HPC and MMC.