Impact of fluorine-containing nanoparticle PEGylation on inflammation imaging by 19F MRI

Fluorine-containing nanoparticles (FNPs) are widely used for inflammation imaging by fluorine-19 magnetic resonance imaging (¹⁹F MRI) due to their biocompatibility and suitability to track immune cells via phagocytic uptake. For targeting approaches beyond passive incorporation, surface PEGylation of FNPs is required to reduce cellular uptake, but is known to prolong blood half-life of the particles. This study investigates the efficacy of FNP PEGylation for inflammation imaging in vivo. FNPs and PEGylated FNPs (^PEGFNPs) of different size were synthesized and characterized for particle properties and fluorine content. Cellular uptake was explored in CHO, RAW, and J774 cells as well as in whole blood using flow cytometry. For in vivo imaging, a murine lipopolysaccharide (LPS)-induced inflammation model was employed, followed by intravenous injection of FNPs or ^PEGFNPs and ¹⁹F MRI to monitor inflammation. PEGylation significantly reduced the uptake of FNPs by macrophages and blood immune cells, as observed through reduced fluorescence and ¹⁹F signals. Despite reduced cellular uptake in vitro, in vivo ¹⁹F MRI showed similar signal intensities in inflamed tissues for both FNPs and ^PEGFNPs, suggesting contributions from both immune cell-associated and non-cell-associated signals for small particles. However, for bigger particles significantly more ¹⁹F signal was observed in inflamed tissue for FNP compared to ^PEGFNP. In conclusion, increase in particle size can abolish the non-specific accumulation of FNPs in inflammatory lesions and additionally increase the phagocytosis of FNPs by murine immune cells. This results in a specific immune-cell dependent ¹⁹F signal with rather no background due to non-specific diffusion.