Tissue distribution and in vivo photosensitizing activity of 13,15-[N-(3-hydroxypropyl)]cycloimide chlorin p6 and 13,15-(N-methoxy)cycloimide chlorin p6 methyl ester.
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 micromol/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 micromol/kg, whereas MMC is 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.
Karmakova
Tatyana
T
Hertsen Moscow Oncological Institute, 2nd Botkinskiy pr., 3, Moscow 125284, Russia.
Feofanov
Alexei
A
Pankratov
Andrei
A
Kazachkina
Natalia
N
Nazarova
Anna
A
Yakubovskaya
Raisa
R
Lebedeva
Victoria
V
Ruziyev
Ramzes
R
Mironov
Andrey
A
Maurizot
Jean-Claude
JC
Vigny
Paul
P
D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D051379:Mice; D018613:Microscopy, Confocal; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D011166:Porphyrins / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*
C509071:13,15-(N-methoxy)cycloimide chlorin p6 methyl ester; C461439:13,15-N-(3'-hydroxypropyl)cycloimide chlorin p6; D017319:Photosensitizing Agents; D011166:Porphyrins