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Blood-brain barrier (BBB) is a specialized structure that regulates molecular passage from the circulatory system into the brain. Focused ultrasound (FUS) combined with intravenously circulating microbubbles can transiently and selectively increase BBB permeability to enable targeted drug delivery to the brain (reviewed in [1]). An overlooked additional application consists in facilitating the entry of brain radiotracers for Positron Emission Tomography (PET), a nuclear imaging technique. In the process of radiotracer development, it is common to reject candidate molecules with high affinity and selectivity because they show poor brain uptake [2]. In the BIORAN team, we have developed a promising radiotracer targeting the serotonin receptor type 6 (5-HT6) [3], which might have crucial implication in obesity and neurodegenerative diseases. However the use of [18F]2FNQ1P in rodent models is hampered by a strong P-gp efflux evidenced by cyclosporine treatment (Fig.1). In collaboration with the Laboratory of Therapeutic Applications of Ultrasound (LabTAU), we aim at testing the ability of focused ultrasound to promote an efficient and reproducible entry of the radiotracer, thus allowing quantitative and longitudinal PET imaging. Practical work will include combined FUS and PET experiments, high-resolution autoradiography, and image analysis.