Metal Ion Complexes for Antibody Imaging and Therapy in Breast Cancer

摘要

The goals of this project were to prepare and test novel bifunctional chelates based on DOTA to anti-CEA and anti-her2/neu antibodies. The conjugates were labeled with In-111 for imaging and Y-90 for therapy. Two tumor xenograft models were tested: MCF7 cell transfected with her2/neu for over-expression of her2/neu, and MCF7 cell expressing 'normal' amounts of her2/neu. Both cell lines also express CEA. We showed that both models had good uptake of In-111 labeled antibodies and responded to Y-90 labeled RIT. The RIT response was further improved by the combined administration of taxol and RIT. Novel peptide-DOTA conjugates to recombinant antibody fragments were prepared, radiolabeled with In-111, and shown to reduce normal kidney uptake compared to DOTA directly conjugated to the same antibody fragments. This work demonstrates that breast cancers can be treated with both anti-her2/neu and anti-CEA antibodies, and that recombinant antibody fragments can be used for imaging or therapy with the novel peptide linker chelators.