Focused ultrasound-enabled delivery of radiolabeled nanoclusters to the pons.

The goal of this study was to establish the feasibility of integrating focused ultrasound (FUS)-mediated delivery of ⁶⁴Cu-integrated gold nanoclusters (⁶⁴Cu-AuNCs) to the pons for in vivo quantification of the nanocluster brain uptake using positron emission tomography (PET) imaging. FUS was targeted at the pons for the blood-brain barrier (BBB) disruption in the presence of systemically injected microbubbles, followed by the intravenous injection of ⁶⁴Cu-AuNCs. The spatiotemporal distribution of the ⁶⁴Cu-AuNCs in the brain was quantified using in vivo microPET/CT imaging at different time points post injection. Following PET imaging, the accumulation of radioactivity in the pons was further confirmed using autoradiography and gamma counting, and the gold concentration was quantified using inductively coupled plasma-mass spectrometry (ICP-MS). We found that the noninvasive and localized BBB opening by the FUS successfully delivered the ⁶⁴Cu-AuNCs to the pons. We also demonstrated that in vivo real-time microPET/CT imaging was a reliable method for monitoring and quantifying the brain uptake of ⁶⁴Cu-AuNCs delivered by the FUS. This drug delivery platform that integrates FUS, radiolabeled nanoclusters, and PET imaging provides a new strategy for noninvasive and localized nanoparticle delivery to the pons with concurrent in vivo quantitative imaging to evaluate delivery efficiency. The long-term goal is to apply this drug delivery platform to the treatment of pontine gliomas.