Pub No:
Application of Benzoporphyrin Derivatives to Photodynamic Therapy 38
Masutani, M., Richter, A.M., David Dolphin, Levy, J., and Horie, T.
Nihon Univ. J. Med.
(1), 51-64
Four benzoporphyrin derivs. (BPDs) were compared for their in vitro and vivo photosensitizing activities with a mixture of dihematoporphyrin ethers/esters (DHE, Photofrin II). The in vitro photosensitizer activity was tested using several tumor cell lines, and it was found that the monoacid derivatives (monoacid ring A, BPD-MA; monoacid ring B, BPD-MB) had an equiv. cytotoxicity and were about 2-5 times more active than the diacids (diacid ring A, BPD-DA; diacid ring B, BPD-DB). All four BPD analogs were found to be more cytotoxic than DHE. In an in vivo/in vitro assay, BPD-MA and DHE achieved cytotoxicities of about 50%, when exposure to light was performed 3 h after injection. However, at 24 h after injection, BPD-MA had lost most of its photosensitizing effect, while DHE retained its ability. These results suggested that the active form of BPD-MA disappeared relatively quickly from the tumors and correlated well with the data for skin photosensitivity, plasma clearance, and elimination of tritiated BPD-MA. BPD-MA caused in vivo destruction of M1 tumors (DBA/2 mouse methylcholanthrene-induced rhabdomyosarcoma) following irradiation with 378 J/cm2 of red light (580-750 nm in wavelength) at both 3 h and 24 h after injection. Its effect was similar to that of DHE. It appeared that microvascular damage rather than direct cytotoxicity for the tumor cells may have been the immediate cause of tumor regression. In conclusion, exposure to light at 3 h rather than 24 h after injection may achieve more effective photodynamic therapy (PDT) when using BPD.

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