Optimization of targeted two-photon PDT triads for the treatment of head and neck cancers

摘要

Synthesis of new PDT triads that incorporate a tumor-killing porphyrin with large two-photon cross-section for 150 fs laser pulses (2000 GM) in the Near-infrared (NIR) at 840 run, a NIR imaging agent, and a small peptide that targets over-expressed EGF receptors on the tumor surface. This triad formulation has been optimized over the past year to treat FADU Head and Neck SCC xenograft tumors in SCID mice. Effective PDT triad dose (1.10 mg/Kg) and laser operating parameters (840 nm, 15-45 min, 900 mW) have been established. Light, dark and PDT treatment toxicities were determined, showing no adverse effects. Previous experiments in phantom and mouse models indicate that tumors can be treated directly through the skin to effective depths between 2 and 5 cm. Treated mice demonstrated rapid tumor regression with some complete cures in as little as 15-20 days. No adverse effects were observed in any healthy tissue through which the focused laser beam passed before reaching the tumor site, and excellent healing occurred post treatment including rapid hair re-growth. Not all irradiation protocols lead to complete cures. Since two-photon PDT is carried out by rastering focused irradiation throughout the tumor, there is the possibility that as the treatment depth increases, some parts of the tumor may escape irradiation due to increased scattering, thus raising the possibility that tumor re-growth could be triggered by small islands of untreated cells, especially at the rapidly growing tumor margins, a problem we hope to alleviate by using image-guided two-photon PDT.