Photodynamic therapies: principles and present medical applications

Photodynamic therapy (PDT) by porphyrins and related tetrapyrrole derivatives is an emerging new treatment modality of tumors of lung, eosophagus and skin and of age-related macular degeneration. Phase III clinical trials for other applications such as re-stenosis after angioplasty are also underway. Under systemic conditions, the transport of porphyrin photosensitizers by serum low density lipoproteins and their specific delivery to tumor cells and vasculature is a determinant of treatment effectiveness. However, this effectiveness can be improved by increasing the selectivity of the photosensitizer uptake by tumors and by using photosensitizers absorbing light in the 660-800 nm range where tissues have the highest transmittance. Another treatment showing great promise is the PDT of skin cancers after topical application of the protoporphyrin IX precursor delta-aminolevulinic acid (or its ester forms). In all the cases, the photosensitizers should be rapidly excreted to avoid a long lasting skin photosensitivity.