Patients with brain tumours have limited treatment options and could benefit from new treatments. Focused ultrasound (FUS) combined with a microbubble agent, under guidance of magnetic resonance (MR) imaging, has been used in animal studies to temporarily open the blood-brain-barrier (BBB). The BBB normally protects the brain by blocking most substances from the blood and is a hurdle to the use of therapeutic agents in the brain. The ability to use FUS induced BBB disruption to target drugs to desired volumes in the brain presents a potentially huge advance for neuroscience. The method can also increase the permeability of the blood-tumour barrier, which often retains many characteristics of the normal BBB. To translate this technique to clinical applications, the effectiveness of the technique should be demonstrated. Patients with no or limited treatment options are probably the most willing candidates to participate in a clinical trial, e.g. breast cancer patients with brain metastases. For extracranial metastases in breast cancer patients two antibody agents have shown good results. Their effectiveness in brain metastases is limited, due to the BBB. Permeabilization of the BBB might improve survival in this group of patients. Animal studies with these drugs will be performed to study the survival and tumour progression in rats. The rats will be divided in different treatment groups, animals that 1) get one or both drugs combined with FUS induced BBB permeabilization; 2) only get one or both drugs; 3) only receive FUS induced BBB permeabilization; and 4) receive no treatment. The results of this project will guide future clinical studies. MRguided FUS for targeted drug delivery in the brain is a new and revolutionary technique, with possibilities in many diseases of the central nervous system. As there is limited research in Europe involving this technique, it is important for the ERA to increase the knowledge in Europe and expand research on this topic.