MORPHOLOGICAL CHANGES OF TUMOR MICROVASCULATURE FOLLOWING HEMATOPORPHYRIN DERIVATIVE SENSITIZED PHOTODYNAMIC THERAPY*

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Abstract
There is increasing evidence that the tumor microvasculature is affected during porphyrin photodynamic therapy. In the following study, the effect of hematoporphyrin derivative photodynamic therapy on tumor microvasculature was studied by electron microscopy. Urothelial tumors, implanted subcutaneously in rats, were exposed to red light (> 590 nm; 360 J cm−2) 72 h after injection of hematoporphyrin derivative at a dose of 5 mg kg−1 of body weight. Prior to sampling, in vivo perfusion was carried out using a polyvalent cation, lanthanum, in 3% glutaraldehyde to define the endocapillary layer of endothelial cells. Samples of tumors were collected at 0, 1,2 and 4 h after completion of photodynamic therapy. Histological changes in endothelial cells were evident immediately following completion of light exposure. Immediate morphological changes included absence of the endocapillary layer as well as mitochondrial degeneration. The changes within tumor cells followed the changes within the microvasculature. This study indicates that the endothelial cell of tumor tissue is an important target of photodynamic therapy and may be responsible for the blood flow changes reported previously.