BIFUNCTIONAL CHELATING AGENTS IN TUMOR LOCALIZATION

  • Meares, Claude F, (PI)

Project: Research project

Project Details

Description

The long-term goal of this project is to develop new ways in which chelated
metal ions may be used in the detection and treatment of cancer.
Bifunctional chelating agents are important to this work; these compounds
contain a powerful metal-chelating group and may be attached covalently to
biological molecules such as monoclonal antibodies or drugs such as
bleomycin. The products form stable chelates with more than 50 chemical
elements; these elements have many useful properties -- such as
radioactivity, paramagnetism, luminescence, and catalytic activity -- which
have current and future applications in medical diagnosis and treatment.
Specific aims are to use newly prepared monoclonal anti-chelate antibodies
to strongly enhance the tumor localization of chelate-tagged bleomycin
analogs and other chelate radiopharmaceuticals, and to investigate the
mechanism(s) by which tumor uptake of chelate-tagged bleomycins is
increased (by an order of magnitude) in the presence of anti-chelate
antibodies. The versatile chemistry of the new BLEDTA IV synthesis --
which links bleomycin to chelators and other groups via coordination to
inert cobalt(III), with no covalent modification of bleomycin -- will be
used to prepare tumor-localizing bleomycin analogs bearing side-chains
which may have cytotoxic properties or act as photoaffinity labels for
mechanistic studies. The use of chelate-tagged antitumor antibodies with
metabolically cleavable linkages between antibody and chelate will be
explored with the aim of improving tumor imaging by reducing background
interference. New bifunctional chelators with macrocyclic structures will
be prepared, aimed at preventing any loss of metal from chelate during
metabolism and thus minimizing potential toxic side effects of certain
procedures. The methodology involves chemical synthesis and purification,
chemical modification of proteins (antibodies), trace metal chelation
chemistry, and a large number of associated analytical procedures. The
proposed studies should provide information relevant to a number of
advanced technical methods, including nuclear medicine, radioimmunotherapy,
nuclear magnetic resonance imaging, and immunoassay.
StatusFinished
Effective start/end date6/1/782/28/11

Funding

  • National Institutes of Health: $190,111.00
  • National Institutes of Health
  • National Institutes of Health: $277,428.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $183,437.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $201,847.00
  • National Institutes of Health: $280,432.00
  • National Institutes of Health: $276,704.00
  • National Institutes of Health: $196,233.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $393,073.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $288,843.00

ASJC

  • Medicine(all)

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