RADIOPHARMACEUTICALS LABELED WITH METAL RADIONUCLIDES

Project: Research project

Project Details

Description

The goal of this project is the development of new and improved
radiopharmaceuticals designed to allow nuclear medicine to exploit the
attractive nuclear properties of a number of metallic radionuclides. The
main focus of the project will be the development of blood flow tracers
labeled with generator-produced positron-emitting nuclides (copper-62 and
gallium-68). Such tracers might facilitate more widespread use of positron
emission tomography (PET) in clinical diagnosis by reducing the dependence
of PET centers on nuclides that require in-house cyclotron production.
Some studies in technetium chemistry are also proposed, again emphasizing
the potential role of these compounds as perfusion tracers. Underlying
these efforts is a desire to elucidate principles of inorganic chemistry
and drug design that might find broad general application in research to
deliver new metal-labeled radiopharmaceuticals. Metal complexes, possessing properties believed to be important for
achieving tissue uptake in proportion to regional rates of blood flow, will
be prepared and characterized at both macroscopic (10-3 10-1M) and tracer
concentrations. These radiolabeled metal complexes will be screened to
evaluate their potential as radiopharmaceuticals by determination of their
biodistribution in rats following intravenous injection. Such studies will
serve to identify the best tracers for further evaluation. In addition,
the biodistribution studies will provide data for the definition of
structure-activity relationships describing the molecular features vital to
tracer uptake and tracer retention in tissues of interest (brain, heart,
kidney, and tumor). The most promising tracers identified in the studies
with rats will be further assessed in animal models by comparison of their
tissue uptake with blood flow measured using standard reference tracers
(labeled microspheres and iodoantipyrine). PET imaging experiments with
the copper-62 tracers already developed will be conducted in collaboration
with Professors Steven R. Bergmann and Marcus E. Raichle at Washington
University, allowing the performance of these compounds to be evaluated
relative to standard cyclotron-produced PET tracers in animal model
systems. Synthetic work with the copper (II) bis(thiosemicarbazone)
complexes already developed will also continue, in order to refine their
preparation into a convenient and reliable kit formulation for use with the
eluent of a copper-62 generator.
StatusFinished
Effective start/end date8/1/876/30/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $229,342.00
  • National Institutes of Health

ASJC

  • Medicine(all)

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