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Distribution, retention, and phototoxicity of hematoporphyrin derivative in a rat glioma. Intraneoplastic versus intraperitoneal injection

Journal Article · · J. Neurosurg.; (United States)
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 (/sup 3/H) 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 /sup 3/H-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 /sup 3/H-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 /sup 3/H-HPD ratios were 3:1 and 32:1, respectively. In all cases, /sup 3/H-HPD was found in every portion of the tumor, even at a distance from the injection site. For the /sup 3/H-HPD doses used in this study, after direct injection both subcutaneous and intracerebral tumor tissue contained about three to four times more /sup 3/H-HPD than tumors in rats receiving intraperitoneal /sup 3/H-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.
Research Organization:
Massachusetts General Hospital, Boston
OSTI ID:
5577022
Journal Information:
J. Neurosurg.; (United States), Journal Name: J. Neurosurg.; (United States) Vol. 5; ISSN JONSA
Country of Publication:
United States
Language:
English