Harness the Power of Upconversion Nanoparticles for Spectral Computed Tomography Diagnosis of Osteosarcoma

Osteosarcoma, as the most common primary bone cancer, is difficult to make a differentiation between tumor with contrast agents (CAs) accumulation and healthy bones using X‐ray computed tomography (CT) since they both display high attenuation of X‐ray. Recently, an advanced CT form, gemstone spectral CT (GSCT), has received extensive attention due to its significant ability of material decomposition and monochromatic images, which can overcome the above disadvantages of conventional CT. Herein, the lutecium (Lu)‐based upconversion nanoparticles (UCNPs, polyethylene glycol (PEG)–NaLuF 4 :Yb/Er), which possess great spectral CT performance over clinical used iohexol, is investigated as a novel kind of spectral CT CAs in the diagnosis of osteosarcoma. Both in vitro and in vivo experiments show that Lu‐based UCNPs provided much more diagnostic interpretation, and can successfully distinguish the osteosarcoma from the surround bones with GSCT while the iohexol fails due to the different X‐ray attenuation characteristics of UCNPs (i.e., lutecium) and iohexol (e.g., iodine) under different energy. As a proof of concept, the Lu‐based UCNPs with excellent biocompatibility hold great potential for further clinical diagnosis of skeletal system diseases.