1 in 8 women will develop breast cancer in the UK. In 25% of cases over-expression of the human epidermal growth factor receptor-2 (Her2) is found, which is an adverse prognostic factor and used to guide therapy selection. Tumour biopsies are unreliable and painful. There is an urgent need now for a non-invasive test which can measure her2 expression reliably. Aims:To evaluate the clinical utility of the novel PET probe GE-226 Affibody ([18F]FBA-ZHER2:2891) in patients with breast cancer. Methodology: An initial method development phase will include 8 patients with her2 positive and 8 patients with her2 negative metastatic breast cancer who will dynamic PET imaging over 90 minutes post-injection of GE-226. Radial arterial sampling will be performed to obtain a kinetic input function. Scans will be reconstructed by iterative and filtered back projection algorithms. Mathematical modelling techniques will determine GE-226 binding, delivery, and retention in tumour and non-tumour tissue. Metabolism of GE-226 will be quantified by HPLC. A tissue specimen will be obtained for immunohistochemistry and silver in situ hybridisation testing to quantify her2 expression and amplification. Safety data will be collected and patients will be monitored for any adverse effects as this is a first in patient study. This study will determine the optimum time-point for imaging for the second phase of the study. The second phase will include a baseline static PET imaging study to be performed in 25 her2 positive patients with metastatic breast cancer who are to be treated with trastuzumab- emtamsine (TDM-1) (standard for this group). Tumour uptake will be quantified by SUV, response will be measured using standard CT imaging and RECIST criteria after 3 cycles of treatment. The study will be performed at 4 of the largest breast cancer units in the UK by leading oncologists and imaging physicians. The results could redefine management of patients with her2 positive cancer.