Focused ultrasound (FUS) to open the blood brain barrier (BBB) is under evaluation for the delivery of therapeutic agents to the brain. Regarding delivery of genes through the BBB, adeno-associated viruses (AAVs) have generated interest due to their ability to specifically and efficiently transfect the brain, which was recently demonstrated in mouse models. In this work, we investigated the use of 1.5 MHz FUS-mediated BBB opening in a mouse model after systemic injection of AAV-like polymer nanoparticles designed to have a 20-nm size and a targeting peptide similar to AAV-PHP.eB. Radiolabeling of the nanoparticles allowed in vivo tracking of the accumulation in the brain following the FUS treatment with positron emission tomography imaging (PET). Significant accumulation was measured in the treated hemisphere with a 1.8-fold enhancement compared to the contra-lateral hemisphere. Our experimental setup optimized for rodents (Verasonics) enables ultrasound imaging, precise targeting with electronic steering, and monitoring of the cavitation activity during the FUS treatment using passive acoustic mapping.