Abstract

We will investigate the biological properties of molecules labeled using bifunctional chelates with the aim of developing clinically useful tumor localizing agents. We will study two new derivatives of bleomycin, BLEDTA II and BLEDTA III, as well as the protein chelate conjugates of transferrin and monoclonal antibodies. Radiotracer kinetics and electron microscope autoradiography will be used to study the binding to putative receptors on the tumor cell surface, the mechanisms of transport into the cell cytosol and the metabolism by the cell. We will use chemical, radiochemical, enzymatic and immunologic strategies to maximize tumor concentration while lowering the blood background using a tumor mouse model of BALB/c mice bearing KHJJ tumor. We will test in vitro and in vivo tumoricidal properties of the best """"""""carriers"""""""", containing Auger or alpha particle emitters, redox groups, photoreactive groups or covalently bound antitumor drugs. The best tumor imaging agents will be selected for the study of dosimetry, sensitivity and specificity of cancer localization in cancer patients.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA028343-08
Application #
3168090
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1980-07-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Lubic, S P; Goodwin, D A; Meares, C F et al. (2001) Biodistribution and dosimetry of pretargeted monoclonal antibody 2D12.5 and Y-Janus-DOTA in BALB/c mice with KHJJ mouse adenocarcinoma. J Nucl Med 42:670-8
Goodwin, D A; Meares, C F (1999) Pretargeted peptide imaging and therapy. Cancer Biother Radiopharm 14:145-52
Goodwin, D A; Meares, C F; Osen, M (1998) Biological properties of biotin-chelate conjugates for pretargeted diagnosis and therapy with the avidin/biotin system. J Nucl Med 39:1813-8
Goodwin, D A; Meares, C F (1997) Pretargeting: general principles; October 10-12, 1996. Cancer 80:2675-80
Goodwin, D A (1995) Tumor pretargeting: almost the bottom line. J Nucl Med 36:876-9
Goodwin, D A; Meares, C F; Watanabe, N et al. (1994) Pharmacokinetics of pretargeted monoclonal antibody 2D12.5 and 88Y-Janus-2-(p-nitrobenzyl)-1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) in BALB/c mice with KHJJ mouse adenocarcinoma: a model for 90Y radioimmunotherapy. Cancer Res 54:5937-46
Watanabe, N; Goodwin, D A; Meares, C F et al. (1994) Immunogenicity in rabbits and mice of an antibody-chelate conjugate: comparison of (S) and (R) macrocyclic enantiomers and an acyclic chelating agent. Cancer Res 54:1049-54
Goodwin, D A; Lang, E V; Atwood, J E et al. (1993) Viability and biodistribution of 68Ga MPO-labelled human platelets. Nucl Med Commun 14:1023-9
Goodwin, D A; Meares, C F; McTigue, M et al. (1992) Pretargeted immunoscintigraphy: effect of hapten valency on murine tumor uptake. J Nucl Med 33:2006-13
Marincola, F M; Drucker, B J; Keeling, C A et al. (1989) The in vivo distribution of human peripheral blood lymphocytes and lymphokine-activated killer cells adoptively transferred in human pancreatic cancer-bearing nude mice. Surgery 105:79-85

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