Double duty: Cancer therapy moonlights as breast tumor imaging agent

Metastatic breast cancers positive for HER2 receptor expression can be effectively imaged with Cu-64 DOTA-trastuzumab, traditionally used as a therapeutic drug, according to a study published online Sept. 12 in the Journal of Nuclear Medicine.

HER2 receptor imaging has been picking up speed in recent years. Researchers including Kenji Tamura, MD, PhD, from the department of breast and medical oncology at the National Cancer Center Hospital in Tokyo tested the feasibility of using the fused radionuclide and humanized monoclonal antibody Cu-64 DOTA-trastuzumab, not as a cancer therapy, but as an imaging agent for metastatic breast cancer screening. Results showed consistent detection of HER2 positive lesions.

“Targeting of HER2 with the monoclonal antibody trastuzumab is a well-established therapeutic strategy for HER2-positive breast cancer in neoadjuvant, adjuvant, and metastatic settings,” wrote Tamura et al. “Although HER2 expression is routinely determined using immunohistochemistry or FISH [Fluorescence In Situ Hybridization], technical problems can arise when lesions cannot be easily accessed by core-needle biopsy. In addition, HER2 expression can vary during the course of the disease and even across tumor lesions within the same patient. Therefore, to overcome these problems, a novel technique such as PET molecular imaging is required for the noninvasive evaluation of HER2 expression.”

For this first-ever human study, six patients with metastatic breast cancer were injected with Cu-64 DOTA-trastuzumab and underwent PET imaging one, 24 and 48 hours after injection. Findings revealed that the agent was not only able to pick up metastatic HER2-positive tumors, but also primary tumors as first evidenced by CT imaging. Blood tests revealed high radioactivity, but low uptake in healthy tissues and an overall dose equivalent to FDG PET. Surprising the researchers, Cu-64 DOTA-trastuzumab was able to pass the blood-brain barrier to show brain metastases as well.

“In a clinical setting, it is not possible to obtain a brain tissue sample without surgery; however, knowledge of the HER2 status would in turn allow the identification of the best additional systemic treatment to control the symptoms of the central nervous system,” wrote the authors. “Although penetration of the blood–brain barrier by trastuzumab is generally considered to be poor, we could visualize brain lesions in this study, probably because of disruption of the blood–brain barrier at the site of brain metastasis or whole-brain radiation.”

In time clinicians may be able to enlist Cu-64 DOTA-trastuzumab for imaging HER2-positive brain tumors, but further study is needed to fully understand both HER2 positive and negative expression in that context.