Biological activities of phthalocyanines. XVII histopathologic evidence for different mechanisms of EMT-6 tumor necrosis induced by photodynamic therapy with disulfonated aluminum phthalocyanine or photofrin

Abstract

The necrosis of EMT-6 mammary murine tumors induced by photodynamic therapy (PDT) with Photofrin (PII) or disulfonated aluminum phthalocyanine (AlPcS2) was studied. Attention was given to the spontaneous evolution of angiogenesis and necrosis of such tumors in order to determine the most appropriate moment for treatment. On day 6 after tumor cell inoculation, mice were injected with photosensitizer followed by exposure to red light 24 h later, at which time optimal dye concentrations were reached in the tumor. Animals were sacrificed 3 h or 24 h after illumination and tissues were prepared for histology. Prominent cytopathic alterations were already observed at 3 h and there was massive necrosis at 24 h. In the case of PII vascular damage, congestion and hemorrhage were already present at 3 h and these changes account for the subsequent tumor necrosis through hemorrhagic infarction. With AlPcS2 these early vascular alterations were much less evident and only focal at 24 h, suggesting that AlPcS2-PDT mediated tumor necrosis involves to a large extent direct tumor cell damage.