Fluorescent microscopy of hematoporphyrin derivative in the nude mouse tumor model

Mechanisms for localization of hematoporphyrin derivative (HPD) within malignant tissue and for tumor necrosis after photodynamic therapy have not yet been established with certainty. We describe a modified freeze-drying technique to study these mechanisms. Normal tissues and squamous cell carcinoma xenografts were examined in nude mice after administration of HPD. Skin reveals marked fluorescence in connective tissue cells. No fluorescence is visible in surface epithelial cells or keratin. Liver shows diffuse fluorescence only in cells lining sinusoids. In tumor, malignant cells do not fluoresce and connective tissue cells fluoresce brilliantly. This technique provides a clear view of HPD fluorescence, frozen instantaneously in location and time. Fluorescence from connective tissue cells in skin and tumor suggests that localization and photodynamic action may be targeted in part at cells that critically support malignant epithelial cell growth as well as at malignant epithelial cells directly.