Development of Cu-loaded Perfluoropentane Nanodroplet: A Potential Tumor Theragnostic Nano-carrier and Dual-Modality PET-Ultrasound Imaging Agents.

The purpose of this study was to develop and preliminarily evaluate phospholipid-shelled nanodroplets (NDs) encapsulating perfluoropentane (PFP) and radioactive Cu as a hybrid positron emission tomography (PET)-ultrasound (US) probe. PFP NDs were fabricated by mixing liquid-phase PFP with a phospholipid solution. The Cu was encapsulated into the NDs in a size-controlled manner by exploiting the hydrophobicity of Cu-diacetyl-bis(N-methylthiosemicarbazone) (Cu-ATSM) using a vial mixer and an extruder. The fabricated Cu-loaded PFP NDs (Cu-PFP NDs) were evaluated using in vitro/in vivo PET-computed tomography (PET-CT), US imaging and transmission electron microscopy. In the in vitro PET images, the Cu-PFP NDs were observed as a hot spot in the lower section of the test tube. In the acquired US images, the mean region of interest brightness values of Cu-PFP NDs were revealed by their strong echo image. In a tumor-bearing mouse animal model, tumor uptake of the Cu-PFP NDs was low, that is, approximately 65%, compared with that of only free Cu, as determined by PET-delayed imaging analysis. The dual-function concept of the NDs is expected to contribute to the prognosis and effectiveness of therapy by fusing the science and technology of nuclear medicine and US.