ABSTRACT
Two problems currently prevent radiopeptides from reaching their full potential in cancer therapy: Low absolute tumor concentrations, and High and prolonged renal uptake. Radiolabeled peptides and mAbs have different advantages and weaknesses for therapy. Specifically, the long circulation time of mAbs is an advantage for producing high absolute tumor uptake. Having several peptides per poly(ethylene)glycol (bPEG) gives a multivalent targeting function with high avidity. The kidney is a major site of metabolism for peptides and uptake has correlated with the size of the peptide or polypeptide rather than its function. The ligand’s low reactivity prevents cross-reactions with other molecules in the medium. However, in the antibody/ligand complex the effective local concentrations of the complementary reactive groups are immense, allowing for a covalent reaction to link the two together. Long circulation of the iAb-bPEG-peptide conjugates may also increase the absolute amount and retention of therapeutic radionuclide in the target tumor.
