Designing Treatment Individualization in Photodynamic Therapy to Compensate for Pharmacokinetic Variability
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چکیده
The main theme of this thesis is to investigate the origins of photosensitizer pharmacokinetic variability, how this pharmacokinetic variation affects photodynamic therapy (PDT), and to search for innovative strategies to reduce the inter-individual pharmacokinetic variability and variability in treatment response. PDT involves photosensitizer administration and light irradiation to the tissue to be destroyed. With this inherent dual selectivity, PDT can have high inter-individual variability in response to treatment, due to the variation in photosensitizer uptake, delivered light dose, and tumor oxygenation. Although light irradiation dosimetry can be achieved to improve the treatment in clinical practice, inter-individual photosensitizer pharmacokinetic variability has not been optimized as extensively. The ability to individualize PDT treatment according individual photosensitizer pharmacokinetics has not yet been investigated. To address this issue in a mechanistic way this study focuses on the microscopic transport pathways of the drug. Both transvascular and interstitial transport processes have been characterized in the Dunning prostate MAT-LyLu tumor model using the drug verteporfin. The dominant factors determining
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