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.

Fluorinated NPs, in vivo <sup>19</sup>F MRS spectra and <sup>19</sup>F MRI images.

Fluorinated NPs, in vivo ¹⁹F MRS spectra and ¹⁹F MRI images.

Dr Monica Carril

Universidad del Pais Vasco - Campus Bizkaia

Appearances