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Computed tomography (CT) is one of the most widespread imaging techniques in clinical use worldwide. CT contrast agents are administered to improve soft tissue contrast and highlight blood vessels. However, the range of CT contrast agents available in the clinic is limited and they suffer from short-circulation times and low k-edge values that result in the need for high doses for in vivo applications. Nanomaterials containing a mixture of electron-dense elements, such as BaYbF 5 nanoparticles, have shown promise as more efficient CT contrast agents, but they require biocompatible coatings for biomedical applications. Here, we explore the use of a bifunctional PEG polymer (5 kDa) containing a terminal bisphosphonate (BP) anchor for efficient binding to the surface of BaYbF 5 nanomaterials. The resulting PEG(5)-BP-BaYbF 5 nanoparticles were synthesized and characterized using TEM, DLS, TGA, XRD and Z-potential measurements. Their in vitro stability was verified and their ability to produce CT contrast in a wide range of X-ray energies, covering preclinical and clinical scanners, was demonstrated. In vitro toxicity studies with PEG(5)-BP-BaYbF 5 in the phagocytic pro-monocytic human cell line U937 did not identify toxic effects, even at high concentrations (30 mM). In vivo, PEG(5)-BP-BaYbF 5 exhibited efficient CT contrast for angiography imaging, highlighting blood vessels and vascular organs, and long circulation times as expected from the PEG coating. However, at late time points (48 h), in vivo toxicity was observed. While the causes could not be completely elucidated, in vitro studies suggest that decomposition and release of Yb 3+ and/or Ba 2+ metal ions after decomposition of PEG(5)-BP-BaYbF 5 may play a role. Overall, despite the promising CT contrast properties, our results suggest that BaYbF 5 nanomaterials may suffer from significant long-term toxicities.

Synthesis and in vivo evaluation of PEG-BP–BaYbF5 nanoparticles for computed tomography imaging and their toxicity

Synthesis and in vivo evaluation of PEG-BP–BaYbF₅ nanoparticles for computed tomography imaging and their toxicity