Radiolabelling of lipid-based nanocarriers with fluorine-18 for in vivo tracking by PET

Organic nanoparticles made out of biodegradable and biocompatible materials have attracted increased attention in the therapeutic and diagnostic fields. In this study, we attempted to explore a new radiolabelling chelating free strategy for biodegradable sphingomyelin nanometric emulsions with fluorine-18 (F-18), a radioisotope regularly used in clinic. [F-18]fluoride was produced by the cyclotron and was incorporated into 4-[F-18]fluorobenzamido-N-ethylmaleimide ([F-18]FBEM), which was coupled next to the emulsions previously functionalized with a thiol group, via inclusion of either a thiol-PEG-lipid (SH-PEG(12)-C-18), or a peptide-PEG-lipid (Cys-Pro-Ile-Glu-Asp-Arg-Pro-Met-Cys-PEG(8)-C-18) derivative. Radiolabelled emulsions were obtained in a rapid and efficient fashion through facile-conjugated chemistry without the use of organic solvents, and characterized in terms of size, polydispersity, surface charge, pH, and osmolarity. PET imaging and biodistribution studies in BALB/c mice allowed obtaining the pharmacokinetics of the radiolabelled emulsions and determining the clearance pathways. Altogether, we confirmed the potential of this new technique for the radiolabelling of lipid-based drug nanosystems for application in PET imaging diagnosis.