Fluorine Labeling of Nanoparticles and In Vivo ¹⁹F Magnetic Resonance Imaging

Fluorinated nanoparticles have increasing applications, but they are still challenging to prepare, especially in the case of watersoluble fluorinated nanoparticles. Herein, a fluorine labeling strategy is presented that is based on the conjugation of custom-made small fluorinated building blocks, obtained by simple synthetic transformations, with carboxylated gold nanoparticles through a convenient phase-transfer process. The synthesis of four fluorinated building blocks with different chemical shifts in 19 F nuclear magnetic resonance and varied functionalities is reported, along with their conjugation onto nanoparticles. Fluorinated nanoparticles of small core size obtained by this conjugation methodology and by direct synthesis presented high transverse relaxation times (T 2 ) ranging from 518 to 1030 ms, and a large number of equivalent fluorine atoms per nanoparticle (340-1260 fluorine atoms), which made them potential candidates for 19 F magnetic resonance related applications. Finally, nontargeted fluorinated nanoparticles were probed by performing in vivo 19 F magnetic resonance spectroscopy ( 19 F MRS) in mice. Nanoparticles were detected at both 1 and 2 h after being injected. F MRI images were also acquired after either intravenous or subcutaneous injection. Their fate was studied by analyzing the gold content in tissues by ICP-MS. Thus, the present work provides a general fluorination strategy for nanoparticles and shows the potential use of small fluorinated nanoparticles in magnetic-resonance-related applications.