Studies were conducted to assess the interdependence of three discrete parameters known to influence hematoporphyrin derivative (Hpd)‐induced photosensitization. The effects of fiuence, drug dose and oxygen environment were examined for their role in causing an inhibition of the activity of mitochondrial cytochrome c oxidase. Experiments were performed on R3230AC mammary tumor mitochondria in vitro and on mitochondria isolated from tumors of animals pre‐treated with Hpd in vivo. Inhibition of cytochrome c oxidase activity was observed to be directly proportional to total energy density. Photosensitization was dependent on oxygen concentration, with total energy density dependent photosensitization being diminished in environments containing less than 5% oxygen. At 1% oxygen environments, photosensitization was significantly impaired and demonstrated no drug‐dose relationship. These results suggest that tissue oxygen concentration may represent a critical factor for the therapeutic usefulness of Hpd photodynamic therapy in treatment of cancer.
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Gibson et al. (1985) studied this question.
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