The feasibility of NaGdF₄ nanoparticles as an x‐ray fluorescence computed tomography imaging probe for the liver and lungs

Abstract

Purpose As a novel imaging modality, x‐ray fluorescence computed tomography (XFCT) can provide distribution and concentration information of contrast agents containing high atomic number elements, such as iodine, gadolinium, barium, gold, and platinum. Since XFCT has a better sensitivity and detection limit of high‐Z elements compared with traditional and spectral CT, it becomes a powerful quantitative imaging tool for biological studies. The main problem of current XFCT imaging is its low emission and detection efficiency of x‐ray fluorescence (XRF) photons. Increasing XRF photons generation by choosing a high atomic element as a contrast agent is essential to improve the imaging quality of XFCT. Gadolinium emits at least a few times more of XRF photons than gold under the same x‐ray excitation condition, leading to a detection limit at a level of sub‐mg/mL as the next generation of clinical imaging modality. However, most current XFCT studies have utilized gadolinium salt as the contrast agent, which could not accumulate in organs or tumors efficiently, making in vivo XFCT imaging quite difficult. In this study, we present NaGdF4 nanoparticles with ultra‐small size as nanoprobes to test the feasibility for in vivo XFCT application for the first time. Methods NaGdF4 nanoparticles with different sizes (3–10 nm) were successfully synthesized via a coprecipitation process by controlling the reaction time at temperature of 290 °C. The morphology, crystal phase, chemical composition, and size of such NPs were further characterized with HR‐TEM, XRD, and EDX. The abilities of XRF photons from different sizes of NPs were quantified by our customized XFCT imaging system. To access the in vivo application of as‐synthesized NPs, such hydrophobic NPs capped OA molecules were further modified with AEP via a ligand‐exchange process and characterized with FT‐IR. For in vivo XFCT imaging, 0.1 mL of 30 mg/mL NPs were injected into nude mice via the tail vein. The Varian G‐297 x‐ray tube was set to 150 kV and 0.5 mA. The XRF photons were captured by a Kromek eV‐3500 photon counting detector at each 8° for 10 s. Result The successfully synthesized NaGdF4 nanoparticles (3–10 nm) were monodisperse, highly uniform spherical morphology and hexagonal crystalline phases. No significant influence on XRF photons yields or XFCT imaging quality were found by varying the nanoparticle size. The XRF photons were 2.5 times more emitted from NaGdF4 nanoparticles (NPs) compared to gold nanoparticles, thereby leading to a better image quality. With the AEP surface modification, such NPs were readily adapted for use in in vivo XFCT applications with monodispersity in aqueous solution and negligible cytotoxicity. With the tail‐vein injection, the liver, spleen, and lungs could be clearly imaged with XFCT at a sub‐mg/mL level. Conclusions Such NaGdF4 NPs, which were synthesized with coprecipitation process, were modified with AEP for in vivo XFCT applications. With both the phantom and in vivo experiments, such NPs were proved to be appropriate probe...

Dual imaging modality of fluorescence and transmission X‐rays for gold nanoparticle‐injected living mice

“…17 In 2020, a benchtop XFCT study with a linear array cadmium zinc telluride (CZT) detector and a single pinhole collimator was reported for in vivo imaging of NaGdF 4 NPs. 18 Fused images of XFCT and CT confirmed the feasibility of NaGdF 4 as a contrast agent for the liver and lungs of mice. However, the validity of the fused images might be questioned because the XFCT and CT images were acquired from different experimental setups.…”

“…The pinhole XRF imaging system, which can directly acquire 2D XRF images without image reconstruction due to pinhole collimator and a 2D CZT gamma camera, could acquire time‐lapse XRF images from the kidneys and bladder of living mice. In addition, it is important to note that unlike the other dual imaging modalities of XRF and CT using single‐crystal or linear array detectors, 8,18–20 a 2D array detector used in this study can address the key technical limitations of single‐crystal or linear array detectors. The use of a 2D array detector has been proved to reduce the excessive image acquisition time and radiation dose during XRF imaging.…”

“…In 2020, a benchtop XFCT study with a linear array cadmium zinc telluride (CZT) detector and a single pinhole collimator was reported for in vivo imaging of NaGdF 4 NPs 18 . Fused images of XFCT and CT confirmed the feasibility of NaGdF 4 as a contrast agent for the liver and lungs of mice.…”

Multifunctional high-Znanoradiosensitizers for multimodal synergistic cancer therapy

“…Nanomaterials with high-Z elements possess a high radiation attenuation coefficient that can deposit highenergy X-rays. [19][20][21] When high-Z nanomaterials are irradiated by X-rays, several physical processes occur (such as Rayleigh scattering, photoelectric effect, and Compton scattering). Meanwhile, various particles, such as photoelectrons, spiral electrons, and recoil electrons produced by RT, interact with the surrounding water to produce a large number of reactive oxygen radicals (ROS), which can damage DNA molecules and improve the efficacy of RT.…”

Simulation Research of Potential Contrast Agents for X-Ray Fluorescence CT with Photon Counting Detectors

“…However, there is no specific contrast agent for XFCT, which mainly used the X-CT contrast agent like gold nanoparticles (GNPs). Liu et al, used Pt as the XFCT contrast agent and verified its feasibility by the Monte Carlo simulation [6]; Gd was commonly used as the X-CT and MRI contrast agent, and Zhang et al used it for XFCT and figured out that the number of fluorescence photons of Gd is two times more than that of Au and imaged it at a sub-mg/mL level [7]; Li et al proposed Ru nanoparticles as the contrast agent of XFCT, and the lowest detectable concentration is 0.2 mg/ml [8]. At the same time, they also proposed other potential fluorescent materials such as Y, Zr, Nb, Rh, and Bi [9].…”