The distribution, retention, and phototoxicity of the sensitizer hematoporphyrin derivative (HPD) were studied following intraperitoneal and direct intraneoplastic injections of the agent into subcutaneous or intracerebral gliosarcomas in rats. Forty-eight hours after intraperitoneal injection, the ratio of tritiated (3H) HPD in subcutaneous tumor: adjacent normal skin was about 1.4:1 and the ratio in tumor: normal brain was 3:1. In contrast, direct injection of 3H-HPD into subcutaneous tumors resulted in tumor: adjacent normal skin concentration ratios of approximately 44:1 and tumor: normal brain ratios of about 61:1. For rats bearing intracerebral gliosarcomas, intraperitoneal administration of 3H-HPD resulted in approximately 1.3-fold sensitization in tumor tissue relative to adjacent edematous brain. In contrast, after direct injection into intracerebral tumors, the tumor: adjacent edematous brain and tumor: skin 3H-HPD ratios were 3:1 and 32:1, respectively. In all cases, 3H-HPD was found in every portion of the tumor, even at a distance from the injection site. For the 3H-HPD doses used in this study, after direct injection both subcutaneous and intracerebral tumor tissue contained about three to four times more 3H-HPD than tumors in rats receiving intraperitoneal 3H-HPD. Both in vitro and in vivo clonogenic assays demonstrated that the photodynamic inactivation of the tumors was significantly greater after direct injection than after intraperitoneal injection.

A B S T R A C T Herpes simplex virus (HSV) types

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