title: Distribution, retention, and phototoxicity of hematoporphyrin derivative in a rat glioma. Intraneoplastic versus intraperitoneal injection.
abstract: 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.
mesh_terms: D000818:Animals; D001929:Brain Edema / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D017324:Hematoporphyrin Derivative; D006414:Hematoporphyrin Photoradiation; D006415:Hematoporphyrins / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use* / Q000633:toxicity; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014316:Tritium
chemical_list: D006415:Hematoporphyrins; D014316:Tritium; D017324:Hematoporphyrin Derivative