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Tumor Targeting Using PEG-m-THPC for Photodynamic Therapy in a Rat Ovarian-Cancer Model

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Tumor Targeting in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

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.

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References

  1. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1996 [see comments]. CA Cancer J Clin 1996; 46:5–27.

    Article  PubMed  CAS  Google Scholar 

  2. Gomer CJ, Dougherty TJ. Determination of [3H]- and [14C]hematoporphyrin derivative distribution in malignant and normal tissue. Cancer Res 1979; 39:146–151.

    PubMed  CAS  Google Scholar 

  3. Chatlani PT, Nuutinen PJ, Toda N, Barr H, MacRobert AJ, Bedwell J, Bown SG. Selective necrosis in hamster pancreatic tumours using photodynamic therapy with phthalocyanine photosensitization. Br J Surg 1992; 79:786–790.

    Article  PubMed  CAS  Google Scholar 

  4. Barr H, Tralau CJ, Boulos PB, MacRobert AJ, Krasner N, Phillips D, Bown SG. Selective necrosis in dimethylhydrazine-induced rat colon tumors using phthalocyanine photodynamic therapy. Gastroenterology 1990; 98:1532–1537.

    PubMed  CAS  Google Scholar 

  5. Weishaupt KR, Gomer CJ, Dougherty TJ. Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. Cancer Res 1976; 36:2326–2329.

    PubMed  CAS  Google Scholar 

  6. Kimel S, Tromberg BJ, Roberts WG, Berns MW. Singlet oxygen generation of porphyrins, chlorins, and phthalocyanines. Photochem Photobiol 1989; 50:175–183.

    Article  PubMed  CAS  Google Scholar 

  7. Bonnett R, White RD, Winfield UJ, Berenbaum MC. Hydroporphyrins of he meso-tetra(hydroxyphenyl)porphyrin series as tumor photosensitizers. Biochem J 1989; 261:277–280.

    PubMed  CAS  Google Scholar 

  8. Bonnett R, Berenbaum M. Porphyrins as photosensitizers. Ciba Found Symp 1989; 146:40–53.

    PubMed  CAS  Google Scholar 

  9. Ben-Hur E, Rosenthal I. The phthalocyanines: a new class of mammalian cells photosensitizers with a potential for cancer phototherapy. Int J Radiat Biol Relat Stud Phys Chem Med 1985; 47:145–147.

    Article  PubMed  CAS  Google Scholar 

  10. Rosenthal I. Phthalocyanines as photodynamic sensitizers. Photochem Photobiol 1991; 53:859–870.

    PubMed  CAS  Google Scholar 

  11. Gomer CJ. Preclinical examination of first and second generation photosensitizers used in photodynamic therapy. Photochem Photobiol 1991; 54:1093–1107.

    Article  PubMed  CAS  Google Scholar 

  12. Pass HI. Photodynamic therapy in oncology: mechanisms and clinical use. J Natl Cancer Inst 1993; 85:443–456.

    Article  PubMed  CAS  Google Scholar 

  13. Testa JR, Getts LA, Salazar H, Liu Z, Handel LM, Godwin AK, Hamilton TC. Spontaneous transformation of rat ovarian surface epithelial cells results in well to poorly differentiated tumors with a parallel range of cytogenetic complexity. Cancer Res 1994; 54:2778–2784.

    PubMed  CAS  Google Scholar 

  14. Hornung R, Fehr MK, Monti-Frayne J, Krasieva TB, Tromberg BJ, Berns MW, Tadir Y. Highly selective targeting of ovarian cancer with the photosensitizer PEG-m-THPC in a rat model [In Process Citation]. Photochem Photobiol 1999; 70:624–629.

    Article  PubMed  CAS  Google Scholar 

  15. Barr H, Bown SG, Krasner N, Boulos PB. Photodynamic therapy for colorectal disease. Intl J Colorectal Dis 1989; 4:15–19.

    Article  CAS  Google Scholar 

  16. Hornung R, Fehr MK, Monti-Frayne J, Tromberg BJ, Berns MW, Tadir Y. Minimally-invasive debulking of ovarian cancer in the rat pelvis by means of photodynamic therapy using the pegylated photosensitizer PEG-m- THPC [In Process Citation]. Br J Cancer 1999; 81:631–637.

    Article  PubMed  CAS  Google Scholar 

  17. Wouters BG, Brown JM. Cells at intermediate oxygen levels can be more important than the “hypoxic fraction” in determining tumor response to fractionated radiotherapy. Radiat Res 1997; 147:541–550.

    Article  PubMed  CAS  Google Scholar 

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© 2002 Springer Science+Business Media New York

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Hornung, R. (2002). Tumor Targeting Using PEG-m-THPC for Photodynamic Therapy in a Rat Ovarian-Cancer Model. In: Pagé, M. (eds) Tumor Targeting in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-167-1_19

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  • DOI: https://doi.org/10.1007/978-1-59259-167-1_19

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-251-3

  • Online ISBN: 978-1-59259-167-1

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