1 in 8 women in the UK will develop breast cancer, 20% of whom will have cancer which is her2 positive - meaning that the tumours have a protein receptor on the surface of the cancer cells. The presence of the her2 receptor has been found to make cancers more aggressive, and generally their outcomes are worse than those tumours that are her2 negative. Her2 positive breast cancer can be treated with drugs such as trastuzumab (otherwise known as Herceptin) which is used in the early stages to reduce the risk of relapse, or in the metastatic stage when the cancer has spread to distant organs to try and control the disease. This study aims to develop a new type of scan for imaging patients with her2 positive breast cancer. The test involves a very small amount of a radioactive chemical (called a tracer), which can bind to the her2 receptor. This tracer can be detected in a PET scanner and used to localise the areas that are her2 positive. At present doctors rely on biopsies of tumours to detect her2, the biopsies can be painful and are not always possible from certain areas of the body for example the biopsy might cause bleeding if the tumour is near a blood vessel. In patients with advanced cancer (meaning that the tumour has spread to distant parts of the body) new drugs have been developed which target the her2 receptor. Compared to standard treatments the newer drugs have significantly higher response rates and have been hailed as breakthroughs in the treatment of her2 positive cancer. However the prognosis for this disease remains poor, and the clinical studies show that between 20 and 50% of patients with metastatic her2 positive cancer will not respond to some of these newer agents. Resistance only becomes apparent after several treatments have been given, and is generally found in CT scans which show either new lesions or that the existing tumour lesions have enlarged in size. The newer drugs do have a significant risk of side effects including low platelets (which help the blood to clot in 12%), and heart toxicity (1%). However for individual patients we cannot predict before the start of treatment if their metastatic tumours will respond to treatment, and it is not possible to biopsy every single lesion. This study will be divided into two phases, in the first phase we will assess whether the tracer is taken up more in her2 positive tumours than her2 negative tumours, this will involve detailed PET scans lasting approximately 90 minutes in 16 patients in total, as the tracer (also known as GE-226) has not been used in this specific form before, we will also study safety by monitoring patients carefully before and after the scans, this phase will all be done in one centre in London (Imperial College) which has particular expertise in this type of study, if this phase is successful and there is no significant toxicity we will proceed to the second phase which will involve 25 patients with her2 positive patients who will have a PET scan with GE-226 in one of four centres (whichever is closest), the PET scan will be done at the start of a course of therapy and compared to standard CT scans which are done before treatment and after 3 cycles of treatment (63 days) to measure if the findings from the PET scan can predict which patients will respond to treatment. We will have regulatory approval from all the relevant committees in place (ethics, radiation, MHRA) before the study can start. The outcomes for this project we hope for are to demonstrate that GE-226 has higher uptake in her2 positive disease, that it is safe and well tolerated, and that it can predict response to treatment. If this is successful then larger studies could be done in the future to confirm this, and eventually this could become a routine test in this group of patients which would help oncologists select the best treatments, and also reduce drug costs for the NHS. The study will be led by leading oncologists and imaging scientists from the UK.