The early detection of bone microdamages is crucial to make informed decisions about the therapy and taking precautionary treatments to avoid catastrophic fractures. Conventional computed tomography (CT) imaging faces obstacles in detecting bone microdamages due to the strong self‐attenuation of photons from bone and poor spatial resolution. Recent advances in CT technology as well as novel imaging probes can address this problem effectively. Herein, the bone microdamage imaging is demonstrated using ligand‐directed nanoparticles in conjunction with photon counting spectral CT. For the first time, Gram‐scale synthesis of hafnia (HfO2) nanoparticles is reported with surface modification by a chelator moiety. The feasibility of delineating these nanoparticles from bone and soft tissue of muscle is demonstrated with photon counting spectral CT equipped with advanced detector technology. The ex vivo and in vivo studies point to the accumulation of hafnia nanoparticles at microdamage site featuring distinct spectral signal. Due to their small sub‐5 nm size, hafnia nanoparticles are excreted through reticuloendothelial system organs without noticeable aggregation while not triggering any adverse side effects based on histological and liver enzyme function assessments. These preclinical studies highlight the potential of HfO2‐based nanoparticle contrast agents for skeletal system diseases due to their well‐placed K‐edge binding energy.

The purpose of the present study was to demonstrate an in vitro proof of principle that spectral photon-counting CT can measure gold-labelled specific antibodies targeted to specific cancer cells. A crossover study was performed with Raji lymphoma cancer cells and HER2-positive SKBR3 breast cancer cells using a MARS spectral CT scanner. Raji cells were incubated with monoclonal antibody-labelled gold, rituximab (specific antibody to Raji cells), and trastuzumab (as a control); HER2-positive SKBR3 breast cancer cells were incubated with monoclonal antibody-labelled gold, trastuzumab (specific antibody to HER2-positive cancer cells), and rituximab (as a control). The calibration vials with multiple concentrations of nonfunctionalised gold nanoparticles were used to calibrate spectral CT. Spectral imaging results showed that the Raji cells-rituximab-gold and HER2-positive cells-trastuzumab-gold had a quantifiable amount of gold, 5.97 mg and 0.78 mg, respectively. In contrast, both cell lines incubated with control antibody-labelled gold nanoparticles had less gold attached (1.22 mg and 0.15 mg, respectively). These results demonstrate the proof of principle that spectral molecular CT imaging can identify and quantify specific monoclonal antibody-labelled gold nanoparticles taken up by Raji cells and HER2-positive SKBR3 breast cancer cells. The present study reports the future potential of spectral molecular imaging in detecting tumour heterogeneity so that treatment can be tuned accordingly, leading to more effective personalised medicine.

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Gastrointestinal (GI) tract is one of the hard-to-reach target tissues for the delivery of the contrast agents and drugs mediated by the nanoparticles due to its harsh environment. Herein, we...

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