Photodynamic therapy with hypericin in a mouse P388 tumor model: vascular effects determine the efficacy

Hypericin, a polycyclic quinone obtained from plants of the Hypericum genus , exhibits strong photodynamic antitumor effects. In the present study, PDT efficacy of hypericin under different conditions was compared in a P388 mo use tumor model. Plasma and tumor drug measurements and assessment of vascu lar damage by fluorescein dye exclusion were performed to determine the rel ative contributions of vascular effects and direct tumor cytotoxicity. Furt hermore, the influence of modifying tumor oxygenation on PDT effect was als o evaluated. Study of PDT efficacy and tissue distribution revealed that PD T efficacy was more dependent on plasma concentration than tumor drug level . Fluorescein dye exclusion indicated the complete microvascular occlusion in the tumor and surrounding skin immediately after effective PDT treatment s, while only a limited vascular occulation was observed after non-effectiv e PDT treatment. It was found that neither tumor hypoxia induced by hydrala zine nor increasing tumor oxygenation achieved by nicotinamide could signif icantly affect the effectiveness of various PDT protocols. These results su ggest that tumor vasculature damage might be the primary mechanism of hyper icin-mediated PDT effect. The existence of this potent secondary vascular e ffect is likely to account for the inability of tumor oxygenation modifiers to affect tumor response after PDT with hypericin.