19F Magnetic Resonance Imaging (19F MRI) based on imaging exogenous fluorinated probes, is a versatile diagnosis technique complementary to conventional 1H MRI. However, the applicability of 19F MRI is currently limited by the detection sensitivity of the MRI technique and the need for high local concentration of fluorine, for which the design of highly fluorinated probes is an active field of research. Despite its interesting features, the prospects of fluorine in nanoparticle (NP) design for nanomedicine are somehow limited by several reasons, namely, (i) the high hydrophobicity of fluorinated molecules, (ii) the sometimes challenging synthesis of those, (iii) the need of high local concentration of fluorine for magnetic resonance (MR) applications and (iv) the usually poor relaxation times due to NP structural design. Thus, examples of fluorinated NPs composed of a metal core and fluorinated ligands that are water soluble are scarce. Herein, two methodologies are presented for their preparation: (i) a direct synthesis method using ad hoc prepared fluorinated ligands and (ii) a fluorine labelling strategy based on the conjugation of custom made fluorinated building blocks with carboxylated gold NPs through a convenient phase transfer process. For the latter method, the synthesis of four fluorinated building blocks with different chemical shift in 19F nuclear magnetic resonance and varied functionalities is presented, along with their conjugation onto NPs. Following these two synthetic methodologies, fluorinated NPs of small core size with very high (above the average) transverse relaxation times (T2) ranging from 518 to 1030 ms and fluorine atoms per NP of up to 1260 atoms are obtained. Such T2 and fluorine content values are challenging to achieve in fluorinated probes and make these NPs potential candidates for 19F MR related applications. Finally, non-targeted fluorinated NPs were successfully probed in vivo both by 19F magnetic resonance spectroscopy (19F MRS) and 19F MRI in healthy mice, and their fate was studied by analysing the gold content in tissues by ICP-MS.

Synthesis of water soluble fluorinated gold nanoparticles and in vivo 19F MRS/MRI

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.