Design and Synthesis of Porphyrins for Targeted Molecular Brachytherapy
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Date
2007-12-21
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Abstract
New approaches are urgently needed for treatment of cancer. The inherent heterogeneity of cells in solid tumors has thwarted most approaches developed to date. A fundamentally new approach, targeted molecular brachytherapy, also known as selective targeted amplified radiotherapy (S.T.A.R.), is attractive conceptually but has not yet been implemented. This new method selectively accumulates radioactive precipitates in tumor sites by systemic treatment of distinct agents in a sequential manner. One of the key agents for such a therapy is a soluble, precipitable reagent (SPR). The essence of this thesis includes design, synthesis and evaluation of porphyrin-based SPRs for the S.T.A.R. method. Three distinct designs of porphyrin-based SPRs were proposed. Synthetic approaches for target SPRs were explored, and several model compounds were synthesized. The development of a new synthetic approach to trans-AB-porphyrins, which are essential structures in the designs of SPRs, is also described in this thesis. Several target SPRs have not yet been synthesized due to synthetic difficulties as well as limitations related to water-solubility or stability of compounds. On the other hand, a diphosphate porphyrin exhibited successful enzymatic conversion from the water-soluble form to a porphyrin precipitate. Future work toward SPRs will focus on new designs that incorporate such diphosphate porphyrins.
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soluble precipitable reagent, porphyrin, targeted molecular brachytherapy, cancer therapy
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Degree
PhD
Discipline
Chemistry
