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In this study, we explore the possible utility of injecting hematoporphyrin derivative (HPD) directly into the tumor as a more effective means of porphyrin administration for photodynamic therapy. A subcutaneously implanted mouse bladder tumor was used as the model. Initially, we compared the tissue distribution of HPD in animals with HPD administered intraperitoneally (I.P.; 20 mg/kg. b.w.) and by direct intratumor injection (I.T., 0.4 mg/cm3 tumor). The concentrations of HPD in tumor and tissues were analyzed at various times after the injection, by 3H-HPD method and by a fluorometric method after dye extraction. Results indicated that at 3 to 96 hours after the administration, HPD levels in tumors were 3 to 15 times higher by I.T. than by I.P. injection, while the concentrations in skin and other tissues were 1.3 to 10 times lower. Consequently, ratios between tumor to skin HPD were up to 100 times higher for I.T. than I.P. injection. Subsequently, the photodynamic effect on tumors treated with I.T. injection of HPD was examined. Tumor cell killing, measured by cell survival, was observed in both the I.T. and I.P. groups to about the same extent, and was dependent on fluence and HPD dosage. There was no significant enhancement of cell killing observed in the I.T. injected tumors, despite 5 to 10 times higher porphyrin levels in these tumors. Histological examination of the effect of PDT on the blood vessels indicated that while cell death accompanied severe hemorrhage in the I.P. injected tumors, in the I.T. tumors there was much less hemorrhage and intact blood vessels remained. This observation suggests that with I.T. administration, direct photodynamic action may play a significant role in the tumor cell killing, in contrast to systemic administration, in which destruction of the blood vessels is believed to be the main cause of tumor destruction. This method of sensitizer administration may have utilities in the treatment of most single lesions that are accessible for direct injections as well as an experimental model for evaluating potencies of new photosensitizers and studying mechanisms involved in photo-destruction of tumors.
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