Research Project
6882409
DESCRIPTION (provided by applicant): Anti-angiogenic therapy is currently one of the most active fields in cancer research. There are four basic approaches to limiting angiogenesis: blocking growth factors, inhibiting matrix proteases, directly targeting endothelial cells, and upregulating endogenous inhibitors. Although there is no simple answer to date for blocking angiogenesis, one approach now in clinical results is targeting integrin receptors (Vitaxin, EMD121974, & SB-265123 which target the alpha v, beta 3 integrin). Since the key biochemical parameter in angiogenesis has not been defined and is likely to be a different biochemical target in different tumor types, a molecular probe for the integrin receptor will be important in guiding the choice of patients for integrin receptor antagonist therapy. Five different molecular weight dextrans will be used to span the spectra of possible permeabilities. One set of dextrans will be labeled with both the RGD peptide and Tc-99m. The other set of dextrans will be labeled with RGE and Tc-99m and will serve as a control because changing the molecular weight of the dextran can result in "localization" that is heavily dependent on the permeability of the molecule rather than the specific binding of the RGD peptide to the integrin receptor. This control molecule will therefore serve as a reference for non-integrin receptor processes much like the "reference tissue" model is used in positron emission tomography (PET) neurochemistry imaging. In that case, a tissue that does not contain the target receptor is used as a reference whereas in this study, the dextran control without the RGD peptide will serve as the reference.
