The long-term objective of this project is to understand, improve, and apply techniques for practical, accurate, and clinically meaningful dosimetry for photodynamic therapy (PDT) of solid tumors. These techniques will account for individual differences in treatment parameters and will permit optimization on a patient-by-patient basis. The parallel strategies of implicit and explicit dosimetry will be pursued. In explicit dosimetry the goal is to measure the """"""""ingredients"""""""" of the photochemical reactions that determine outcome. These include photosensitizer concentration, excitation light fluence, and tissue oxygenation. Implicit dosimetry relies instead on the measurement of a surrogate for biological damage, such as the reduction in the fluorescence emitted by photosensitizer molecules during PDT. Four specific alms will be pursued to advance knowledge in both dosimetry paradigms. The first specific aim is to determine whether the implicit parameter of photosensitizer fluorescence photobleaching can predict the survival of cancer cells after PDT. Using cell suspensions as the biological model allows control of all the variables associated with a PDT treatment. Several drugs and cell types of interest to the overall program will be tested. In the second specific aim a more complex biological model, U87 human glioma tumors implanted in rat brain, will be employed. Apoptosis and necrosis will be assessed histologically following PDT with aminolevulinic acid (ALA). The correlation of these endpoints with sensitizer photobleaching will be determined. The third specific aim will be directed to explicit dosimetry of interstitial PDT with the experimental photosensitizer, TOOKAD. Methods based on implanted optical fibers will be developed to measure the optical properties of Dunning prostate minors as well as the intra-tumor concentration of TOOKAD. The ability of these measurements to predict the extent of necrosis will be tested. Finally, in the fourth specific aim, infrared phosphorescence from TOOKAD will be measured in Dunning prostate tumors using an implanted optical fiber. Phosphorescence intensity and lifetime will be assessed as predictors of PDT treatment outcome.
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