ACTIVATION OF BENZOPORPHYRIN DERIVATIVE IN THE CIRCULATION OF MICE WITHOUT SKIN PHOTOSENSITIVITY

In vitro experiments with benzoporphyrin derivative monoacid ring A (B PD) confirmed earlier studies that it was taken up rapidly (within 30 min) to maximum concentrations by all cells tested. It was also confir med that rapidly dividing tumor cell lines and mitogen-activated murin e T lymphocytes took up significantly more (5-10-fold) BPD than did no rmal splenic lymphocytes. Further experiments were undertaken to deter mine whether BPD could be activated by whole-body irradiation with red light in the blood of animals, shortly after intravenous (i.v.) admin istration, in the absence of skin photosensitivity. It was found that shaved and depilated mice injected i.v. 60 min earlier with BPD at bet ween 0.5 and 1.0 mg/kg could tolerate 160 J/cm(2) of broad-band red li ght (560-900 nm) delivered, at a relatively low rate, over a 90 min ti me interval without developing skin photosensitivity or general photot oxicity. During the treatment time, plasma levels of BPD were between 0.7 and 1.0 mu g/mL. The light treatment resulted in between 70 and 80 % photoinactivation of circulating BPD. When L1210 tumor cells were pr eincubated with BPD and injected i.v. into mice immediately before tot al-body light treatment (160 J/cm(2) of 590-900 nm light delivered ove r 90 min), significant reductions in circulating clonogenic tumor cell s were observed in blood samples taken immediately following treatment . This indicated that sufficient light was being delivered to BPD in t he blood flowing in the peripheral vasculature to effect cytotoxicity to cells containing the photosensitizer without causing either vascula r or skin photosensitivity. Thus, activation of this photosensitizer i n the circulation can be achieved by transdermal light exposure withou t causing skin photosensitivity provided that light exposure is perfor med at a time when the first phase of plasma clearance is complete and when the drug has not yet accumulated in skin.