The effect of photodynamic therapy with Benzoporphyrin derivative monoacid ring A (BPD-MA) in three different murine tumors

Photodynamic therapy (PDT), which destructs a neoplastic tissue by the excitation light delivery to the tumor after administration of tumor-specific photosensitizers, is expected an effective local anti-tumor treatment. Recently, various new agents have been developed for improving their tissue penetration potential and for decreasing side effects, such as photosensitive dermatitis. In this study, in vitro cellular uptake of BPD-MA was examined in cell lines of three different murine tumors including B16F1 (melanoma), LM8 (osteosarcoma with high metastatic potential to the lung) and KLN205 (squamous cell carcinoma). Photodynamic in vivo effects of BPD-MA, which was activated by the light at the wavelength of 690nm, were also evaluated at two different timing, 15 minutes and 3 hours, after the intravenous injection of the drug into mice bearing one of these three tumors. Intracellular concentrations of BPD-MA in three cell lines were measured before and 1, 3, 6, 12 and 24 hours after incubation in the media with BPD-MA at the concentration of 1, 2 or 4 mg/ml. Of these cell lines, the largest amount of cellular uptake of BPD-MA was seen in B16F1. That of KLN205 was likely to be larger than that of LM8. Growth of tumorous tissues in tumor-implanted mice, which were treated with photodynamic therapy with BPD-MA, was monitored. Maximum anti-tumor effects were seen in KLN205 treated by either drug-light intervals of PDT. LM8 tumor seemed to be more tolerant to PDT than that of B16F1. In mice with these tumors, 15 minutes drug-light interval PDT, which would target on angiogenesis of tumorous tissue, was more effective than 3 hours interval PDT, which should be standard and had direct effects on the tissue. In conclusion, effects of PDT were obviously different in three tumor cell lines. Simple correlation between in vitro cellular uptake of the drug and in vivo anti-tumor effect was not detected. These results may suggest that photodynamic effects in anti-tumor treatment would largely depend on features of tumor cells and not on intracellular concentration of the drug. Angiogenic PDT protocol would be much more effective than PDT against tumor cells in destruction of tumor tissues.