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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.

Abstract??Mammography is a well-established method for detecting primary breast cancer; however, it has some limitations that may be overcome using nuclear imaging methods. Current radiopharmaceuticals have limited sensitivity for detecting small primary lesions and it has been suggested that novel radiopharmaceuticals are necessary for detection of primary breast cancer, as well as for detecting metastases and recurrence, or for monitoring therapy. The gastrin-releasing peptide receptor (GRPR) is a seven-transmembrane G-protein coupled receptor that is overexpressed on primary breast cancer and lymph node metastases. Bombesin (BN) is a tetradecapeptide that binds with high affinity to GRPR and can be radiolabeled with the positron-emitter, copper-64 (64Cu) for imaging with positron-emission tomography (PET). The goal of this study was to evaluate BN analogs that could be radiolabeled with64Cu for PET imaging of breast cancer. A series of BN analogs containing 4, 5, 6, 8, and 12- carbon linkers were evaluated with regard to their binding and internalization into T-47D human breast cancer cells. The64Cu-labeled analogs were then evaluated in mice bearing T-47D xenografts by tissue biodistribution and microPET imaging. These studies showed that all of the analogs had IC50values <100?nM and were all internalized into T-47D cells. Biodistribution studies showed that the BN analog with the 8-carbon linker not only had the highest tumor uptake but also had high normal tissue uptake in the liver. The analogs containing the 6- or 8-carbon linkers demonstrated good tumor uptake as determined by microPET imaging. Overall, this study shows the feasibility of using positron-labeled BN analogs for PET detection of GRPR-expressing breast cancer. [ABSTRACT FROM AUTHOR]