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)

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A newly synthesized diethylene glycol functionalized chlorin-type photosensitizer, lemuteporfin, was characterized for use in photodynamic therapy (PDT) in a panel of in vitro and in vivo test systems. The photosensitizer was highly potent, killing cells at low nanomolar concentrations upon exposure to activating light. The cellular uptake of lemuteporfin was rapid, with maximum levels reached within 20 min. Mitogen-activated lymphoid cells accumulated more of the lemuteporfin than their quiescent equivalents, supporting selectivity. Photosensitizer fluorescence in the skin increased rapidly within the first few minutes following intravenous administration to mice, then decreased over the next 24 h. Skin photosensitivity reactions indicated rapid clearance of the photosensitizer. Intravenous doses as low as 1.4 micromol/kg combined with exposure to 50 J/cm2 red light suppressed tumor growth in a mouse model. In conclusion, this new benzoporphyrin was found to be an effective photosensitizer, showing rapid uptake and clearance both in vitro and in vivo. This rapid photosensitization of tumors could be useful in therapies requiring a potent, rapidly accumulating photosensitizer, while minimizing the potential for skin photosensitivity reactions to sunlight following treatment.

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