Targeted radiotherapy began in the 1960''s with the identification of CEA, as a tumor associated antigen. In the late 1970''s and early 80''s antibody targeted imaging of adenocarcinomas saw its first clinical trials. Since then both imaging and therapy of tumors based on targeting a tumor- associated molecule has grown. Only recently, radioimmunotherapy for Non Hodgkins lymphoma has become a clinical reality. Targeted therapy has now evolved with the use of a number of new radioisotopes for therapy including Yttrium-90, Rhenium-188 and Rhenium-186, Lutetium-177 and even alpha emitters. Furthermore, the molecules used to target the radiation to tumors have been modified. They have been made smaller, less immunogenic, and bifunctional. In therapy, a number of different strategies have been developed. The strategy that Molecular Targeting laboratory at NYU has chosen to explore has been to combine radioimmunotherapy with agents that will enhance the effect of the targeted radiation at the tumor site. Conversely, low dose radiation delivered by tumor targeting molecules might act to enhance the effect of other anti-tumor agents. Currently, laboratory is exploring the role of topoisomerase I inhibitors in combination with Y-90 antibody for the treatment of ovarian cancer and the role of capecitabine in combination with Y-90 antibody in breast cancer. In addition to optimizing schedules of administration, we are exploring mechanisms of synergy as well as the role of apoptosis, cell cycle regulation, and tumor environment.

In the area of imaging, the laboratory is currently working to radiolabel a peptide that binds in tumor matrix. This peptide has been shown to slow tumor growth, inhibit tumor cell adhesion, angiogenesis, and tumor invasion. The aim is to develop a radiolabeled peptide for imaging to assess the therapeutic potential of the peptide in tumors and possibly characterize the biology of tumors. The approach has been twofold: first to label using and established HYNIC technique and then to go on and optimize a tripeptide approach to binding lanthanides.