A Library of Potential Nanoparticle Contrast Agents for X-Ray Fluorescence Tomography Bioimaging

Abstract

Nanoparticles (NPs) have been used as contrast agents for several bioimaging modalities. X-ray fluorescence (XRF) tomography can provide sensitive and quantitative 3D detection of NPs. With spectrally matched NPs as contrast agents, we demonstrated earlier in a laboratory system that XRF tomography could achieve high-spatial-resolution tumor imaging in mice. Here, we present the synthesis, characterization, and evaluation of a library of NPs containing Y, Zr, Nb, Rh, and Ru that have spectrally matched K-shell absorption for the laboratory scale X-ray source. The K-shell emissions of these NPs are spectrally well separated from the X-ray probe and the Compton background, making them suitable for the lab-scale XRF tomography system. Their potential as XRF contrast agents is demonstrated successfully in a small-animal equivalent phantom, confirming the simulation results. The diversity in the NP composition provides a flexible platform for a better design and biological optimization of XRF tomography nanoprobes.

Synthesis and Cytotoxicity Studies on Ru and Rh Nanoparticles as Potential X-Ray Fluorescence Computed Tomography (XFCT) Contrast Agents

“…The lowest visible NP concentrations agreed with what has been observed in our previous small-animal XFCT experiments [1], indicating the potential capacity of the presented Rh and Ru NPs as XFCT contrast agents in small-animals. From a contrast perspective, the metallic Ru and Rh NPs suffer from higher background noise compared to those based on Y, Zr, Nb and Mo oxide NPs, reported earlier [1,4]. However, the metallic NPs have benefits that include a smaller size (<10 nm) and facilitated surface functionalization.…”

“…XFCT performance was evaluated on a small-animal-sized phantom model, demonstrating the possibility of quantitative evaluation of the measured dose with an expected linear response. This work provides a detailed route for the synthesis, size control and characterization of two materials systems as viable contrast agents for XFCT bio-imaging.(Rh) elements has shown them as promising XFCT contrast agent platforms owing to their spectrally matching Kα edge energies to the liquid-metal-jet X-Ray source [4].Ru and Rh NPs have received much attention mainly for their application as catalysts in hydrogenation, ethanol steam reforming and CO oxidation, as well as for their use in electronics and optics [5]. In addition, some Ru and Rh organometallic complexes have been used in biological applications for their luminescence properties [6].…”

“…(Rh) elements has shown them as promising XFCT contrast agent platforms owing to their spectrally matching Kα edge energies to the liquid-metal-jet X-Ray source [4].…”

Biological laboratory x-ray microscopy

“…Imaging of model cells exposed to a varying concentration of nanoparticles will reveal whether the particles enter into the cells, if they dissolve, or if they accumulate in certain parts. The study can be extended to include several types of nanoparticles, which are currently being developed for XFCT [139].…”

Optical and X-ray Fluorescent Nanoparticles for Dual Mode Bioimaging

“… 5 , 6 Furthermore, the potential use of Rh and Ru based NPs as XFCT contrast agents has also been demonstrated. 7 , 8 With an established library of potential contrast agents for XFCT, an increase in the functionality of the NPs is a natural step.…”