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Title: Efficacy of antitumoral photodynamic therapy with hypericin: relationship between biodistribution and photodynamic effects in the RIF-1 mouse tumor model
Authors: Chen, Bin
Xu, Yan
Roskams, Tania
Delaey, Els
Agostinis, Patrizia
Vandenheede, Jackie
de Witte, Peter # ×
Issue Date: Jul-2001
Publisher: Wiley-Liss
Series Title: International Journal of Cancer vol:93 issue:2 pages:275-82
Abstract: We investigated the hypericin-mediated PDT effects on the tumor and normal skin and in correlation with its biodistribution. These studies were carried out on C3H mice bearing RIF-1 tumors. The hypericin distribution and PDT effects were recorded at different intervals (0.5-24 hr) after intravenous injection of a 5-mg/kg dose of hypericin. After administration, rapid biphasic exponential decay was observed in the plasma drug concentration. It was found that hypericin was preferentially bound to the plasma lipoproteins. The tumor drug levels increased rapidly over the first few hours and reached a maximum around 6 hr after injection. In contrast, PDT efficacy was maximal when irradiation was performed at 0.5 hr after hypericin administration, which led to 100% cure. The PDT efficacy decreased rapidly as the administration-irradiation interval was prolonged. No tumor cure was obtained at the 6-hr interval, even though it was at this time that the tumor drug level peaked. Fluorescence microscopic studies showed that hypericin was mainly confined within the tumor vasculature at 0.5 hr after injection, whereupon it rapidly diffused to the surrounding tumor tissue. At 6 hr, a strong hypericin fluorescence was observed in the tumor tissue with only faint fluorescence within the vasculature, whereas at 24 hr the fluorescence in the tumor also decreased and became more diffused, and no fluorescence could be seen in the tumor vasculature. Like the tumor response, skin reactions were also found to be much more dramatic at short administration-irradiation intervals. Hypericin distribution and PDT response studies revealed a close correlation between the plasma drug level and the PDT effects, which suggests that vascular damage is the primary effect of hypericin-mediated PDT in this tumor model.
URI: 
ISSN: 0020-7136
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
Biochemistry Section (Medicine) (-)
Laboratory for Pharmaceutical Biology (-)
Laboratory of Cell Death Research & Therapy
× corresponding author
# (joint) last author

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