TUMOR PHOTOTHERAPY--NEW PHOTODYNAMIC SENSITIZERS

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The hypothesis to be tested in the continuation of this collaborative project is that phototherapy is applicable to the treatment of highly pigmented tumors such as cutaneous malignant melanoma (CMM). This hypothesis is to be evaluated by (a) establishing the limits of photodynamic therapy (PDT) in pigmented tumors, (b)establishing whether PDT can be applied to melanotic tumors that have been prebleached by high- peak-power light, and (c) establishing the usefulness of photothermal therapy (PTT) to such tumors. The hypothesis will be tested by synthesizing a series of near-IR-light absorbing photosensitizing compounds for PDT and for HT and assaying their effectiveness. Compounds to be synthesized will be metallo-centered naphthalocyanines having various axial and peripheral substituents that will provide solubility and tumor retention modifications. Photophysical measurements will address questions about the nature, lifetime, and deactivation modes of low-lying electronic states and will assist in characterizing the capabilities of the compounds to act in the PDT and HT modes. Pharmacokinetic studies will address the distribution of potential sensitizers for PDT and HT within murine systems (B16 malignant melanoma); and phototherapeutic tests will determine the effectiveness of the various sensitizers and allow the design of protocols for clinical evaluation.