Our long-term objective is to apply the chemistry of N- substituted porphyrins to the development of specific DNA alkylators and imaging agents for gamma scanning and positron emission tomography (PET). DNA alkylators and especially those which cross link DNA are potent cytotoxic agents and have been useful for cancer therapy.
One aim i s to link N-alkylporphyrins (which are potent alkylators of high specificity) to known DNA intercalators to localize the alkylating agent in the vicinity of the DNA bases. Diagnostic imaging by gamma or positron emission uses a small dose of radioactive material to determine the position of abnormal tissue, lesions or blockages, avoiding exploratory surgery. For gamma imaging, N-substituted porphyrins have been bound to antibodies and 67Cu has been rapidly and firmly complexed. Thorough purification and characterization and studies of the distribution of radiolabelled porphyrin-monoclonal antibody adducts will be undertaken. Many isotopes are potentially useful for PET scanning. Beginning with studies of 64Cu complexes, the possibility of imaging inflamed lymph nodes, lung-localized antigen and tumor tissue will be investigated by comparisons of biodistribution data and PET scans. The characteristics of metalloporphyrins formed with other metallic isotopes (such as those of cobalt, nickel and indium) will be determined.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA025427-09
Application #
3166867
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1981-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1991-06-30
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Hunter College
Department
Type
Schools of Arts and Sciences
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065
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Roberts, J C; Adams, Y E; Tomalia, D et al. (1990) Using starburst dendrimers as linker molecules to radiolabel antibodies. Bioconjug Chem 1:305-8
Cole, D A; Mercer-Smith, J A; Schreyer, S A et al. (1990) The biological characteristics of a water soluble porphyrin in rat lymph nodes. Int J Rad Appl Instrum B 17:457-64
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Roberts, J C; Figard, S D; Mercer-Smith, J A et al. (1987) Preparation and characterization of copper-67 porphyrin-antibody conjugates. J Immunol Methods 105:153-64
Lavallee, D K; Fawwaz, R (1986) The synthesis and characterization of 111In hematoporphyrin derivative. Int J Rad Appl Instrum B 13:639-41