Approaches to improved antibody- and peptide-mediated targeting for imaging and therapy of cancer

Abstract

Antibodies with their ability to selectivity bind antigens have been of great interest in targeting radiation, drugs and toxins to tumors. Limited success in delivery of radioactivity has been enjoyed with conventional attachment to antibodies. This is due to slow tumor targeting processes and slow disappearance from blood and variable uptake and disappearance from the excretory organs, liver and kidney. Preliminary studies in animal models and patients have shown promise in increasing the tumor to blood exposure ratio by pretargeting antibody followed by small molecule delivery of radioactivity using a molecular capture system. Efficient capture of the small molecule radioactivity carrier by tumor localized antibody and rapid clearance and excretion of the untargeted radioactivity decreases the background problem for imaging and lowers marrow toxicity for radioimmunotherapy. Small peptide ligands that bind to receptor bearing tumors offer similar advantages.