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.