Molecular Markers for Tissue Hypoxia

DESCRIPTION (PROVIDED BY APPLICANT): Hypoxia is important in cardiovascular
disease and cancer, the two leading causes of death in the US. Studies of these
and other diseases need a tool for following changes in tissue hypoxia. We
propose the HypoxyprobeTM system of markers can meet this need. HypoxyprobeTM
markers have advantages of high water solubility, chemical stability, short
plasma half-life, universal tissue distribution, efficient tissue uptake, low
human toxicity in single and repeated injections and high marker adduct
stability in tissue. Monoclonal antibodies will be prepared against seven
HypoxyprobeTM analogues using techniques already established in our
laboratories. Antibody reagents will be screened in ELISA assays. Sensitivity
of HypoxyprobeTM analogues to hypoxia will be determined in tissue and
multicellular spheroid cultures. Promising analogues will be tested in rodent
and canine tumors in a STTR Phase II study. Leading experts believe that
fluctuating hypoxia is an important factor in the pathophysiology of both
normal and tumor tissues. Interventions designed to offset the damaging effects
of fluctuating hypoxia are under investigation and the present proposal will
provide powerful tools to support studies in these important areas of medicine.
PROPOSED COMMERCIAL APPLICATION:
NPI, Inc has already commercialized Hypoxyprobe (TM)-1, the lead compound in the
Hypoxyprobe (TM) series of markers. It is expected that Hypoxyprobe(TM) analogues
and associated monoclonal antibodies will also be widely used in the study of normal
and tumor tissue hypoxia.