Photodynamic therapy with lasers may become an attractive adjunctive modality for early diagnosis and treatment of superficial malignancies when fluorochromes with high tumor specificity and low toxicity are developed.
The specific aims of this study are to: 1. Develop a noninvasive, simple, accurate, and reproducible quantitiative method of dosimetry of laser induced damage in tissues. The beam scan technique will be developed to measure spatial profiles of laser beams. An infrared camera will allow measurement of thermal profiles in the porcine skin model after exposure to increasing levels of laser energies. Volume of damage will be quantitated by serial histological sections. Damage range constant, absorption coefficients and thresholds for lesions for the CO2, Argon and Nd:YAG lasers will be predicted. The """"""""LAD"""""""" (laser absorptive dose) parallel to the RAD in radiology will be determined. 2. Define the basic intracellular events in laser """"""""killing"""""""" of Rhodamine-123 sensitized human squamous carcinoma and melanoma cells in-vitro. Mitochondrial function, membrane potential and morphology will be assessed respectively by measuring oxygen consumption, 86Rb, 3H-thymidine assays and electron microscopy. ATP levels after laser and Rhodamine-123 phototherapy will be quantitated by luciferin-luciferase assays allowing measurement of mitochondrial oxidative phosphorilation. 3. Establish a randomized clinical protocol which will allow us to test the potentials of this new fluorochrome for the treatment of superficial malignancies of the head and neck with the Argon laser. Patients with recurrent Stage IV tumors (squamous cell carcinoma, melanoma) will be injected with a nontoxic, sensitizing dose of Rhodamine-123, then subjected to low energy Argon laser therapy. Optimal tumor response will be assessed according to the histological type, tumor size, dosages of Rhodamine-123, various laser energies and frequency of treatment. Potential local and systemic toxicity of Rhodamine- 123 will be evaluated. Our study promises to provide relevant information toward the elucidation of the mechanism of action of this promising new photochemosensitizing agent, and will define the potentials for treatment of human head and neck tumors. Furthermore, the basic unit of dosimetry that will be developed with the lasers (""""""""LAD"""""""") will allow standardization of scientific clinical and biomedical research.
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