Radiolabeled Herceptin to Increase Treatment Efficacy in Breast Cancer Patients with Low Tumor HER-2/neu Expression

摘要

The primary objective of the proposal is to evaluate the efficacy and feasibility of using radiolabeled Herceptin antibody to target rapidly accessible breast carcinoma cells or micrometastases. By using Herceptin to specifically deliver radiation we anticipate that the efficacy of Herceptin will be extended to include breast cancer cells that are not high HER-2/neu antigen expressors. This hypothesis will be tested using the spheroid model to simulate rapidly accessible micrometastases. An alpha-particle emitting radionuclide will be used to enhance tumor cell kill. Tasks 1-6 have been completed. The animal model previously used towards task 5 was a HER-2/neu expressing ovarian carcinoma. The PI has identified an appropriate disseminated breast carcinoma animal model and used this to satisfy tasks 5 and 6. Because the PI (Sgouros) relocated in 2003 progress was been delayed. A sub-contract was established with Hopkins to complete the tasks of the proposal. The sub- contract mechanism is being used because after discussions with the contracting officer this was deemed the most expeditious approach to providing funds for the Pt to complete the work at Hopkins. Dr. Sgouros recently received a favorable priority score (156, 8.5%ile) on an NIH RO1 grant application to extend these initial studies to more detailed pre-clinical studies that would incorporate dosimetry and modeling.