Light and drug dosimetry considerations in porphyrin precursor–based photodynamic therapy

Abstract

This thesis concerns light and drug dosimetry for photodynamic cancer treatment – a treatment modality where a photosensitizer uses the energy of light to damage biological matter. Porphyrin precursors were used as prodrugs which are synthesized into photosensitizers inside cells. Human subjects were studied as a part of developing a treatment for non-melanotic skin cancer. A 3-hour application of a topical cream photosensitized the tumor tissue with good selectivity versus normal skin, which suffered only mild phototoxic reactions after light exposure. Longer application times increased the photosensitizer content mainly in normal skin and superficial layers of the tumors. Light exposure using a filtered halogen lamp was found to be as efficient as a laser. A rat model was used to explore treatment of malignant brain tumors using systemic drug application. The intracranial light and photosensitizer distributions were mapped in detail. Treatment with low light dose rates was far more effective than with high dose rates. Significant tumor damage could be achieved with low dose rates, but the experiments suggested insufficient photosensitization of the tumor cells invading normal brain tissue.