Abstract
The human epidermal growth factor receptor 2 (HER2/neu) is overexpressed in 20–30% of breast cancers and is associated with tumor growth, angiogenesis, and development of distant metastases. Trastuzumab, an anti-HER2 monoclonal antibody, is used for the treatment of HER2 positive breast cancer and clinical efficacy of this agent is dependent on HER2 expression. Targeted PET imaging of HER2 with radiolabeled trastuzumab may be used to determine HER2 expression levels and guide therapy selection. The purpose of the current study was to evaluate a facile 89Zr-trastuzumab preparation method that can be efficiently applied for clinical grade production. Also, relative HER2 expression levels in orthotopic and metastatic breast cancer models were assessed by PET imaging using the 89Zr-trastuzumab produced by this simpler method.
Highlights
The human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor (EGFR) tyrosine kinase family [1]
Trastuzumab was successfully conjugated to Df-Bz-NCS and radiolabeled with 89Zr
Data are shown as cell number on the ordinate access and HER2/neu intensity on the abscissa
Summary
The human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor (EGFR) tyrosine kinase family [1]. Heterodimerization of HER2 with other members of the EGFR family promotes cell proliferation, survival, and migration. The association of HER2 with resistance to hormone therapy, chemotherapy, and conventional radiation therapy makes it an attractive target for breast cancer treatment [2,3,6]. The standard of care for locally advanced HER2 positive breast cancer is combination treatment with trastuzumab, chemotherapy, and radiation therapy [8]. An improvement in survival was seen in patients with HER2 positive metastatic disease receiving trastuzumab [9,10]
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