Abstract

Photodynamic therapy (PDT) seems destined for clinical application for a variety of solid tumors. PDT involves the use of a photosensitizer which can be activated in vivo by penetrating light. As in most new therapies, many basic questions regarding mechanisms of action are poorly understood. This proposal addresses certain these questions. It has the following aims: 1. Mechanism of uptake and retention of the active photosensitizer in hematoporphyrin derivative, tentatively identified as dihematoporhyrin ether (DHE); 2. Why the vasculature of tumors is a major target of PDT; 3. What tissue factors influence tissue response to PDT; 4. Can the drug and light dose be varied to improve therapeutic ratio in PDT; 5. To improve instrumentation for detection of very small or very deep tumors via porphyrin fluorescence.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA016717-17
Application #
3164477
Study Section
Radiation Study Section (RAD)
Project Start
1987-09-15
Project End
1993-05-31
Budget Start
1991-06-01
Budget End
1993-05-31
Support Year
17
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14263

  Publications

Mayhew, E; Vaughan, L; Panus, A et al. (1993) Lipid-associated methylpheophorbide-a (hexyl-ether) as a photodynamic agent in tumor-bearing mice. Photochem Photobiol 58:845-51
Henderson, B W; Owczarczak, B; Sweeney, J et al. (1992) Effects of photodynamic treatment of platelets or endothelial cells in vitro on platelet aggregation. Photochem Photobiol 56:513-21
Henderson, B W; Sumlin, A B; Owczarczak, B L et al. (1991) Bacteriochlorophyll-a as photosensitizer for photodynamic treatment of transplantable murine tumors. J Photochem Photobiol B 10:303-13
Kessel, D; Dougherty, T J; Truscott, T G (1988) Photosensitization by diporphyrins joined via methylene bridges. Photochem Photobiol 48:741-4
Waldow, S M; Henderson, B W; Dougherty, T J (1987) Hyperthermic potentiation of photodynamic therapy employing Photofrin I and II: comparison of results using three animal tumor models. Lasers Surg Med 7:12-22
Potter, W R; Mang, T S; Dougherty, T J (1987) The theory of photodynamic therapy dosimetry: consequences of photo-destruction of sensitizer. Photochem Photobiol 46:97-101
Mang, T S; Wieman, T J (1987) Photodynamic therapy in the treatment of pancreatic carcinoma: dihematoporphyrin ether uptake and photobleaching kinetics. Photochem Photobiol 46:853-8
Dougherty, T J; Mang, T S (1987) Characterization of intra-tumoral porphyrin following injection of hematoporphyrin derivative or its purified component. Photochem Photobiol 46:67-70
Miller, A C; Henderson, B W (1986) Effect of DL-buthionine-S,R-sulfoximine on the growth of EMT6 and RIF mouse tumors. J Natl Cancer Inst 77:505-10
Miller, A C; Henderson, B W (1986) The influence of cellular glutathione content on cell survival following photodynamic treatment in vitro. Radiat Res 107:83-94

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