Efficacy of antitumoral photodynamic therapy with hypericin: Relationship between biodistribution and photodynamic effects in the RIF-1 mouse tumor model

We investigated the hypericin-mediated PDT effects on the tumor and normal skin and in correlation with its biodistribution. These studies were carrie d out on C3H mice bearing RIF-I 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 bipha sic 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 reache d a maximum around 6 hr after injection. In contrast, PDT efficacy was maxi mal when irradiation was performed at 0.5 hr after hypericin administration , which led to 100% cure, The PDT efficacy decreased rapidly as the adminis tration-irradiation interval was prolonged, No tumor cure was obtained at t he 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 hype ricin fluorescence was observed in the tumor tissue with only faint fluores cence within the vasculature, whereas at 24 hr the fluorescence in the tumo r also decreased and became more diffused, and no fluorescence could be see n in the tumor vasculature, Like the tumor response, skin reactions were al so found to be much more dramatic at short administration-irradiation inter vals, Hypericin distribution and PDT response studies revealed a close corr elation between the plasma drug level and the PDT effects, which suggests t hat vascular damage is the primary effect of hypericin-mediated PDT in this tumor model. (C) 2001 Wiley-Liss, Inc.