Preclinical examination of first and second generation photosensitizers used in photodynamic therapy.

Numerous photosensitizers with absorption peaks spanning the 600-800 nm "therapeutic window" have been and continue to be synthesized. Structural modifications of the dyes can then be made in order to improve tumor deliverability and retention. Chemical alterations can also enhance the yields of light generated reactive oxygen species. Utilization of lipoproteins, emulsions and antibody conjugates can enhance the selectivity of drug localization. Most cell types and subcellular structures are highly photosensitive and biochemical analysis indicates that cellular target sites associated with PDT correlate with photosensitizer location. In vivo data suggest that vascular and direct tumor cell damage as well as systemic and local immunological reactions are involved in PDT responsiveness. Additional mechanistic, synthetic and developmental studies are required in order to fully appreciate the potentials of PDT. However, continued enthusiasm and support for basic PDT research (as observed during the past 8 years) will depend to a large extent on the outcome of the current clinical trials.