Wavelength-dependent effects of benzoporphyrin derivative monoacid ring A in vivo and in vitro.
Benzoporphyrin derivative monoacid ring A (BPD-MA) is a chlorin-like photosensitizer currently in clinical trials for cancer and psoriasis. It has maximal absorption peaks at both 630 and 690 nm and can be activated at both these wavelengths. In vitro phototoxicity tests using the P815 murine mastocytoma cell lines conducted over wavelengths of light between 678 and 700 nm emitted by an argon-ion pumped dye laser showed that equivalent cell kill could be achieved between 682 and 690 nm. Tests on in vivo phototoxicity of normal skin of DBA/2 mice injected with 2 mg/kg of BPD-MA and exposed to light at 125 J/cm2, between 620 and 700 nm, demonstrated peaks of normal skin damage occurring at 630-640 nm and 680-690 nm. In tests carried out with light between 620 and 700 nm, at 10 nm increments, it was seen that light delivered at 680-690 nm caused slightly more damage to normal skin than light delivered at 630-640 nm. When lower doses of light between 675 and 705 nm were tested using smaller increments, it was determined that equivalent skin damage occurred over a range of 680-695 nm. Antitumor efficacy in tumor-bearing DBA/2 mice was tested between 683 and 695 nm. It was found that equivalent antitumor efficacy, determined by assessing tumor-free status at 20 days posttreatment, occurred at wavelengths between 685 and 693 nm.(ABSTRACT TRUNCATED AT 250 WORDS)
Waterfield
E M
EM
Quadra Logic Technologies (QLT) Inc., Vancouver, BC, Canada.
Renke
M E
ME
Smits
C B
CB
Gervais
M D
MD
Bower
R D
RD
Stonefield
M S
MS
Levy
J G
JG
D000818:Animals; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D007834:Lasers; D008027:Light; D008297:Male; D012515:Mast-Cell Sarcoma / Q000188:drug therapy*; D051379:Mice; D008811:Mice, Inbred DBA; D010778:Photochemotherapy; D011166:Porphyrins / Q000627:therapeutic use* / Q000633:toxicity*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C504224:benzoporphyrin D