An Early Investigation of Ytterbium Nanocolloids for Selective and Quantitative “Multicolor” Spectral CT Imaging

Abstract

We report a novel molecular imaging agent based on Ytterbium (Yb) designed for use with Spectral “multi-color” Computed Tomogrphy (CT). Spectral CT or multi-ycolored CT provides all of the benefits of traditional CT, i.e., rapid tomographic X-ray imaging, but in addition, it simultaneously discriminates metal-rich contrast agents based on the elements unique x-ray K-edge energy signature. Our synthetic approach involved the use of organically soluble Yb(III)-complex to produce nanocolloids of Yb of noncrystalline nature incorporating high density of Yb (>500K/nanoparticle) into a stable metal particle. The resultant particles are constrained to vasculature (~200nm) and are highly selective for binding fibrin in the ruptured atherosclerotic plaque. Nanoparticles exhibited excellent signal sensitivity and the spectral CT technique uniquely discriminates the k-edge signal (60keV) of Yb from calcium (bones). Bio-elimination and preliminary bio-distribution studied reflected the overall safety and defined clearance of these particles in a rodent model.

K-edge ratio method for identification of multiple nanoparticulate contrast agents by spectral CT imaging

“…To reduce the morbidity and mortality caused by cancer and many other diseases, endeavours spanning technological innovations in imaging systems to the development of nanoparticulate (NP) materials aim at improving clinical diagnosis and therapy planning. Numerous high-atomic-number agents have been investigated for X-ray imaging applications, such as bismuth [1], gold [2], platinum [3], tungsten [4], tantalum [5], hafnium [6], lutetium [7], ytterbium [8], erbium [9], holmium [10], osmium [10] and gadolinium [11]. Moreover, NP CT contrast agents proved to be promising in the context of molecular imaging owing to their higher diagnostic efficacy than current contrast agents [12][13][14].…”

“…It is the nature of K-edge methods to be highly dependent on bins location, which is owing to the fact that in K-edge imaging methods, the main aim is to identify contrast agents by considering their unique K-edge energies. In most previously proposed K-edge imaging approaches, the energy thresholds of bins have been adjusted so that they are placed very near to the K-edge energy of a given contrast agent [8,19,33,43,44]. This indicates that in the presence of multiple contrast agents, increasing the number of contrast agents decreases the energy bins width an increase in the quantum noise and streak artefact in the bin images owing to photon starvation.…”

Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches

“…[266] To partly solve bioelimination and preliminary biodistribution issues Yb nanocolloids were used as spectral CT contrast agents.…”

Integration of imaging into clinical practice to assess the delivery and performance of macromolecular and nanotechnology-based oncology therapies

“…Recent efforts aimed at achieving higher tumor contrast enhancement and imaging sensitivity have motivated the development of nanoparticle-based imaging contrast agents. Nanoparticle-based CT contrast agents include atoms of high atomic number with superior X-ray attenuation capabilities, such as gold [96], Gd [97], iodine [98], bismuth [99], and ytterbium [100]. Encapsulation, coating or functionalization of these atoms can be leveraged to increase biocompatibility, prolong circulation half-life, and enable conjugation with targeting moieties for tumor-specific delivery and uptake.…”