This proposal presents a binary system for the treatment of cancer using boron neutron capture therapy (BNCT). Boron-10, when activated by thermal neutrons, produces a fission reaction yielding highly destructive alpha particles. Incorporation of sufficient boron into structures that have a proclivity for melanoma cells is described. Monoclonal antibodies directed against melanoma-associated antigens will be covalently linked to boron-containing macromolecules. These together with other tumor-localizing compounds such as boron-containing chlorpromazine and porphyrins, either alone or in combination will be evaluated for their ability to deliver a critical number of boron-10 atoms (about 10-9) per cell and sustain a lethal n,Alpha reaction in vitro. Once this has been established, their in vivo tumor localizing properties will be determined in melanoma-bearing mice. These studies will lay the ground work for chemoradiotherapeutic trials in animals.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA041288-01A1
Application #
3181625
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1986-09-01
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Pharmacy
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Tzeng, J J; Barth, R F; Orosz, C G (1992) Quantitation of glioma-reactive cytolytic T lymphocyte precursors by means of limiting dilution analysis. J Immunol Methods 146:177-84
Oredipe, O A; Barth, R F; Rotaru, J H et al. (1992) Lack of effect of recombinant human interferon-alpha 2b on expression of 17-1A antigen on human colon cancer cells. Hybridoma 11:607-15
Barth, R F; Adams, D M; Soloway, A H et al. (1991) Determination of boron in tissues and cells using direct-current plasma atomic emission spectroscopy. Anal Chem 63:890-3
Tzeng, J J; Barth, R F; Orosz, C G et al. (1991) Phenotype and functional activity of tumor-infiltrating lymphocytes isolated from immunogenic and nonimmunogenic rat brain tumors. Cancer Res 51:2373-8
Tzeng, J J; Barth, R F; Johnson, C W et al. (1990) Distinct and non-cross-reactive epitopes are recognized on B16 melanoma by LAK cells and anti-B16 monoclonal antibodies. Proc Soc Exp Biol Med 193:285-92
Oredipe, O A; Barth, R F; Rotaru, J H et al. (1990) Alterations in monoclonal antibody affinity and antigenic receptor site expression on mycoplasma-infected human colorectal cancer cells. Proc Soc Exp Biol Med 194:301-7
Barth, R F; Soloway, A H; Fairchild, R G (1990) Boron neutron capture therapy of cancer. Cancer Res 50:1061-70
Soloway, A H; Alam, F; Barth, R F et al. (1990) Tumor targeting agents for neutron capture therapy. Basic Life Sci 54:37-47
Alam, F; Soloway, A H; Bapat, B V et al. (1989) Boron compounds for neutron capture therapy. Basic Life Sci 50:107-11
Barth, R F; Soloway, A H; Alam, F et al. (1989) Pre-clinical studies on boron neutron capture therapy. Basic Life Sci 50:95-105

Showing the most recent 10 out of 12 publications