Distribution, retention, and phototoxicity of hematoporphyrin derivative in a rat glioma

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.

Increased efficacy of photodynamic therapy of R3230AC mammary adenocarcinoma by intratumoral injection of Photofrin II

“…misonidazole (Gonzalez et al, 1986;Winther et al, 1988) (Kostron et al, 1986;Lin et al, 1988a, b) , 1986), response of the mouse MBT-2 bladder tumour was not enhanced, even though 5-10 times more porphyrin was present in tumours after i.t. injection (Lin et al, 1988 a, b).…”

“…Two features of PDT are noteworthy. The hydrophobic components (Dougherty, 1987;Kessel et al, 1987) of Photofrin II (presumably di-haematoporphyrin ethers and/or esters) are retained for longer periods in tumour tissue than in most normal tissues (Gomer & Dougherty, 1979;Kostron et al, 1986;Steichen et al, 1986;Lin et al, 1988a), resulting in a favourable tumour to normal tissue ratio of photosensitiser. By creating a therapeutic window at selected times after drug administration, irradiation would produce minimal deleterious effects in the surrounding normal tissues due to their reduced porphyrin content.…”

Uptake and kinetics of 14C-labelled meta-tetrahydroxyphenylchlorin and 5-aminolaevulinic acid in the C6 rat glioma model

“…Compared with the photosensitizing properties of porphyrins (Kaye et al, 1985;Kostron et al, 1986) m-THPC has significantly higher concentrations in our tumour model. We could find a brain-tumour ratio of over 1:80 between 36 and 48 h.…”

“…PDT has been used to kill glioma cells in vivo and in vitro, and selective uptake of the first-generation photosensitizer haematoporphyrin derivate (HPD) into cerebral tumours has been demonstrated (Wise and Taxdal, 1967;Kaye et al, 1985;Kostron et al, 1986).…”

Photodynamic therapy with intratumoral administration of Lipid‐Based mTHPC in a model of breast cancer recurrence

“…Penetration of those drugs following topical application is shallow and PDT must be limited to superficial disease [6]. Intratumoral (IT) injection of first generation photosensitizers has been proposed earlier for cerebral or bladder tumors in order to maximize intratumoral photosensitizer load, minimize damage to adjacent healthy organs and reduce skin sensitisation due to the reduced total amount of administered photosensitizer [7][8][9].…”