WAVELENGTH‐DEPENDENT EFFECTS OF BENZOPORPHYRIN DERIVATIVE MONOACID RING A in vivo AND in vitro

Publisher Website
Google Scholar
Abstract
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 P8 15 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 DBN2 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 68–95 nm. Antitumor efficacy in tumor‐bearing DBN2 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. When tumor‐bearing animals injected with BPD‐MA at 2 mdkg and exposed to light 3 h later were treated with either 630 or 690 nm light at various doses, it was observed that 690 nm light was more effective at tumor ablation than was 630 nm light, demonstrating that while similar damage to normal skin may be effected by equivalent doses of light at either wavelength, tumor ablation was greater at 690 nm. Further, our data suggest that alternative light sources with bandwidths greater than those of the argon‐ion pumped dye laser (±0.3 nm) may have equivalent efficacy with this photosensitizer.