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Inorganic nanomaterials based on heavy elements represent a new class of contrast agents for X-ray computed tomography (CT). Recent advances have shown that these materials are highly suited for CT imaging due to their high density and X-ray absorption capabilities. In this contribution, we demonstrated that tungsten oxide (WO3) nanoparticles coated by poly-ε-caprolactone (PCL) can be used as efficient contrast agent for CT imaging. The obtained particles were characterized by electron microscopy (TEM and SEM), and dynamic light scattering (DLS). We also validated their use for enhanced in vivo imaging, since these nanoparticles were observed to display high X-ray attenuation properties and circulation time (up to 3 h), permitting blood pool imaging., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Micro-computed tomography (micro-CT) is an emerging imaging modality, due to the low cost of the imagers as well as their efficiency in establishing high-resolution (1-100 μm) three-dimensional images of small laboratory animals and facilitating rapid, structural and functional in vivo visualization. However use of a contrast agent is absolutely necessary when imaging soft tissues. The main limitation of micro-CT is the low efficiency and toxicity of the commercially available blood pool contrast agents. This study proposes new, efficient and non-toxic contrast agents for micro-CT imaging. This formulation consists of iodinated vitamin E (α-tocopheryl 2,3,5-triiodobenzoate) as an oily phase, formulated as liquid nano-emulsion droplets (by low-energy nano-emulsification), surrounded by a hairy PEG layer to confer stealth properties. The originality and strength of these new contrast agents lie not only in their outstanding contrasting properties, biocompatibility and low toxicity, but also in the simplicity of their fabrication: one-step synthesis of highly iodinated oil (iodine constitutes 41.7% of the oil molecule weight) and its spontaneous emulsification. After i.v. administration in mice (8.5% of blood volume), the product shows stealth properties towards the immune system and thus acts as an efficient blood pool contrast agent (t(1/2) = 9.0 h), exhibiting blood clearance following mono-exponential decay. A gradual accumulation predominantly due to hepatocyte uptake is observed and measured in the liver, establishing a strong hepatic contrast, persistent for more than four months. To summarize, in the current range of available or developed contrast agents for preclinical X-ray imaging, this agent appears to be one of the most efficient., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The in vivo X-ray micro-computed tomography (micro-CT) is a very powerful and non-invasive tool used to establish high-resolution images with isotropic voxels in typical scan times ranging from minutes to tenths of minutes. This preclinical imaging technology is primarily adapted to visualize bones. X-ray imaging of soft tissues is made possible by using opaque compounds, providing contrast through tissue vascularization. Thus, using control agents with a long-lasting time in the blood, active or passive targeting of soft tissue is made possible in small animals. In this respect, the use of hydrophilic iodinated X-ray contrast media remains limited due to their rapid blood clearance, albeit at a slightly slower pace in humans as compared with rodents. The development of an iodinated contrast medium with increased vascular residence time is thus necessary. This is precisely the scope of the present paper, which will review and compare in detail the different vectors used as long-circulating iodinated contrast agents for micro-CT, i.e. liposomes, nanoemulsions, micelles, dendrimers and other polymeric particles. The discussion is focused, for each of these nanoparticulate systems, on their method of formulation and production, their stability properties, encapsulation properties, release properties, pharmacokinetics, and toxicology. The different aspects relative to the adaptation of these properties and physico-chemical characteristics for blood pool contrast agents aimed at angiographic micro-CT applications are also discussed. The aim of this review is to propose an overview into the formulation and properties of iodinated micro-CT contrast agents for preclinical applications., (2010 Elsevier Ltd. All rights reserved.)