New Imaging Modality for Early Detection of Breast Cancer

Institution: University of California, Los Angeles
Investigator(s): William Pardridge, M.D. -
Award Cycle: 1995 (Cycle I) Grant #: 1IB-0006 Award: $49,516
Award Type: IDEA
Research Priorities
Detection, Prognosis and Treatment>Imaging, Biomarkers, and Molecular Pathology: improving detection and diagnosis



Initial Award Abstract (1995)
This work attempts to develop a non-invasive diagnostic test that allows for the early detection of breast cancer. This new approach will merge three methodologies in the biological sciences: tumor-specific proteins called monoclonal antibodies; x-ray imaging of these antibodies, which are tagged with radioactivity; and a chemical modification of the antibody, called "cationization" which gives the antibody electric charge. The novel feature of the proposed work is the use of "charged" antibodies as imaging probes for human breast cancer. The original promise of monoclonal antibodies as "magic bullets" has not been realized for a variety of reasons. However, a significant factor is the lack of access of the monoclonal antibody in the blood to the tumor antigen buried within the breast tumor. This lack of access is due to the fact that antibody proteins are too large in size to escape the blood circulation and do not effectively enter into the cancerous tissue from the blood.

The present application will use a new antibody delivery technology that allows circulating antibodies to rapidly escape from the blood to enter the tumor tissue. A specific antibody will be used in these studies, and this antibody targets a specific protein that is produced by many breast cancers. After the "cationization" modification of the antibody, it will be tagged with radioactivity. The tumor uptake of the antibody can then be detected by technologies available in standard x-ray clinics, such as single photon emission computed tomography (SPECT).

It is possible that following both the cationization and radioactive tagging, the antibody will no longer recognize the breast cancer protein. Therefore, these studies will test the feasibility of making these modifications in the antibody in such a way that the antibody's high affinity for the target protein is retained. If these studies give positive results, then an entirely new approach to the early detection of breast cancer will have been developed.


Final Report (1997)
This project began work intended to develop a non-invasive diagnostic test that allows for the early detection of breast cancer. It merged three methodologies in the biological sciences: tumor-specific proteins called monoclonal antibodies, x-ray imaging of these antibodies tagged with radioactivity, and a chemical modification of the antibody called "cationization." Cationization alters the antibody's electric charge and this allows antibodies to undergo transport across biological membranes. The original promise of monoclonal antibodies as "magic bullets" has not been realized. A significant factor is the lack of access of the monoclonal antibody in the blood to the tumor antigen buried within the breast tumor. This lack of access is due to the fact that the antibody proteins are too large in size to escape the blood circulation and do not effectively enter into the cancerous tissue from the blood.

The present work used a new antibody delivery technology that allowed circulating antibodies to rapidly escape from the blood to enter the tumor tissue. A specific monoclonal antibody called the humanized 4D5 was used in these studies, and this antibody targeted a specific protein that is produced by many breast cancers called the p185 HER2 protein. After the "cationization" modification of the anti-p185 HER2 antibody, it was tagged with [125I]-iodine radioactivity. The tumor uptake of the antibody was detected by standard radioisotope quantitation technology.

The results of these studies showed that the anti-p185 HER2 monoclonal antibody could be cationized and radioactively tagged and the antibody still recognized the breast cancer protein. Two different cell lines were examined, the SK-BR3 human breast carcinoma cell line, and a mouse 3T3 fibroblast line that was transfected with the p185 HER2 activated gene. Future continuation of these studies may lead to a new imaging modality for the early detection of breast cancer.