Zr-89 bevacizumab could be a player in PET detection of breast cancer

Breast cancer tumors often express vascular endothelial growth factor (VEGF)-A and a method of detection involving PET and the monoclonal antibody tracer Zr-89 bevacizumab is showing promise for the assessment of early to late stage primary malignancy, according to a study published May 7 in the Journal of Nuclear Medicine.

Sietske B.M. Gaykema, a research scientist in the department of medical oncology at the University Medical Center Groningen in Groningen, The Netherlands, and colleagues, evaluated Zr-89 bevacizumab’s diagnostic value for primary breast cancer by conducting a data analysis of Zr-89 bevacizumab PET imaging studies of the breast confirmed by VEGF-A assay of enzyme-linked immunosorbent. Results showed that all histologically confirmed malignancies were found with Zr-89 bevacizumab PET except one that was 10mm diameter in size.

“Various studies have reported overexpression of VEGF-A in the breast cancer microenvironment, compared with normal breast tissue,” wrote Gaykema et al. “All VEGF-A splice variants are bound by the clinically used monoclonal antibody bevacizumab. When labeled with the PET isotope Zr-89 bevacizumab preserves its VEGF-A–binding properties. Thus, tracer dosages of radiolabeled bevacizumab can be used for tumor-specific, whole-body imaging of VEGF-A.”

A phantom study was performed to set detection limits of the PET/CT system. Comparative analysis for the 23 patients with breast adenocarcinoma and no prior history of breast cancer showed PET with Zr-89 bevacizumab detected 25 out of 26 breast tumors. Results indicated higher maximum standard uptake value in tumors versus normal breast tissue.

“To our knowledge, this was the first clinical feasibility study with 89Zr-bevacizumab PET in breast cancer patients,” the authors wrote. “Uptake of Zr-89 bevacizumab was visualized in 96.1 percent of the primary tumor lesions, and there was a relation with the level of VEGF-A in the tumor. This result provides proof that Zr-89 bevacizumab might be potentially valuable for biologic characterization of tumors and for prediction and evaluation of the effect of VEGF-A–targeting therapeutics.”

VEGF-A imaging could be used for detection and management of all stages of breast cancer. The only limiting factor mentioned was the increased radiation dose associated with this form of PET mammography compared to x-ray. One cited study estimated that PET involved 15-30 times higher radiation-induced cancer incidence than from conventional mammography. Bevacizumab has the potential to be conjugated with near-infrared florescent dye IRDye 800CW, and studies are already underway to assess its feasibility as a low-radiation alternative.