Abstract

The use of photodynamic therapy for the treatment of cancer is a rapidly growing technique. Specifically the method depends on the incorporation of a photosensitizer (currently hematoporphyrin derivative [HpD]) into the tumor. Subsequent irradiation of the target tumor with light results in the generation of singlet oxygen, a reactive species which destroys the tumor. We have synthesized a new class of photosensitizers which have advantages over hematoporphyrin derivative. This class of compounds, called purpurins, absorb more efficiently than HpD at the longer wavelength of visible light currently used in the photodynamic treatment of cancer. Additionally, purpurins can be synthesized with a high degree of purity and with a known chemical structure. Our goals are to 1) synthesize purpurin analogues to be used for the photodynamic treatment of malignant tumors; 2) study the biologic effects on neoplastic tissue of these analogues when combined with visible light; 3) study the tissue distribution of these analogues; 4) study the biologic effects of these analogues on normal tissue when combined with visible light.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043006-02
Application #
3184868
Study Section
Radiation Study Section (RAD)
Project Start
1986-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Toledo
Department
Type
Schools of Arts and Sciences
DUNS #
City
Toledo
State
OH
Country
United States
Zip Code
43606

  Publications

Morgan, A R; Skalkos, D; Garbo, G M et al. (1991) Synthesis and in vivo photodynamic activity of some bacteriochlorin derivatives against bladder tumors in rodents. J Med Chem 34:2126-33
Selman, S H; Qin, B S; James, H R et al. (1990) Hemodynamic effect of the metallopurpurin SnET2 and light on transplantable FANFT induced bladder tumor. J Urol 143:630-3
Morgan, A R; Garbo, G M; Keck, R W et al. (1990) Synthesis and in vivo activity of some porphyrindione derivatives with potential in photodynamic therapy. J Photochem Photobiol B 6:133-41
Morgan, A R; Cheng, L S; Skalkos, D et al. (1990) Tin etiopurpurin dichloride-sensitized lipid photooxidation of erythrocyte membranes. Photochem Photobiol 52:987-91
Morgan, A R; Garbo, G M; Keck, R W et al. (1990) Metallopurpurins and light: effect on transplantable rat bladder tumors and murine skin. Photochem Photobiol 51:589-92
Morgan, A R; Garbo, G M; Keck, R W et al. (1990) Diels-Alder adducts of vinyl porphyrins: synthesis and in vivo photodynamic effect against a rat bladder tumor. J Med Chem 33:1258-62
Morgan, A R; Rampersaud, A; Garbo, G M et al. (1989) New sensitizers for photodynamic therapy: controlled synthesis of purpurins and their effect on normal tissue. J Med Chem 32:904-8
Kreimer-Birnbaum, M (1989) Modified porphyrins, chlorins, phthalocyanines, and purpurins: second-generation photosensitizers for photodynamic therapy. Semin Hematol 26:157-73
Morgan, A R; Garbo, G M; Keck, R W et al. (1988) New photosensitizers for photodynamic therapy: combined effect of metallopurpurin derivatives and light on transplantable bladder tumors. Cancer Res 48:194-8
Borland, C F; McGarvey, D J; Morgan, A R et al. (1988) Laser flash photolysis of purpurins: novel potential photosensitizers of interest in photodynamic therapy. J Photochem Photobiol B 2:427-34

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