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Tumor targeting using PEG-m-THPC for photodynamic therapy in a rat ovarian cancer model
Book Chapter - Jan 1, 2002
Hornung René
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Malignant pelvic tumors contribute to 36% of all new cancer cases and to 16% of all cancer-related deaths (1). Ovarian cancer is the most lethal of the gynecological malignancies (1). There is a strong need to develop new tumor-debulking techniques, suitable for open surgical procedures with curative intent, as well as for minimally invasive palliative procedures that can be used in combination with chemo- or radiotherapy. Photodynamic therapy (PDT) is currently being evaluated as an adjuvant to surgery, radio-, and chemotherapy for the treatment of malignant tumors. PDT is based on the preferential uptake and/or retention of a photosensitizer by malignant tissues (2–4). Irradiation of the tissue containing the photosensitizer with light of appropriate wavelength leads to oxidation-mediated tissue necrosis (5, 6). Many photosensitizers have been tested for their capability to preferentially localize in malignant tissue, commonly expressed as the tumor to tissue ratio (TTR). Porphyrin derivatives are the most commonly administered photosensitizers. Modifications to the porphyrin structure (7,8) have produced the “second-generation-photosensitizers,” including phthalocyanines (9,10) and chlorins (11) with TTR-values ranging from 1:1 to 5:1 (12). Mesotetra(hydroxyphenyl)chlorin (m-THPC) is an example of a chlorin photosensitizer with promising properties. The addition of four long hydroxyl (polyethylene glycol; PEG) side chains to m-THPC produces a tetrakis-(m-methoxypolyethylene glycol) derivative of 7, 8-dihydro-5,10,15,20-tetrakis(3-hydroxyphenyl)-21–22-[H]-porphin (PEG-mTHPC), which is highly hydrophilic.