Contrast Agents For X-ray Imaging Research Articles

Renally Excretable Silver Telluride Nanoparticles as Contrast Agents for X-ray Imaging.

The use of nanoparticles in the biomedical field has gained much attention due to their applications in biomedical imaging, drug delivery, and therapeutics. Silver telluride nanoparticles (Ag2Te NPs) have been recently shown to be highly effective computed tomography (CT) and dual-energy mammography contrast agents with good stability and biocompatibility, as well as to have potential for many other biomedical purposes. Despite their numerous advantageous properties for diagnosis and treatment of disease, the clinical translation of Ag2Te NPs is dependent on achieving high levels of excretion, a limitation for many nanoparticle types. In this work, we have synthesized and characterized a library of Ag2Te NPs and identified conditions that led to 3 nm core size and were renally excretable. We found that these nanoparticles have good biocompatibility, strong X-ray contrast generation, and rapid renal clearance. Our CT data suggest that renal elimination of nanoparticles occurred within 2 h of administration. Moreover, biodistribution data indicate that 93% of the injected dose (%ID) has been excreted from the main organs in 24 h, 95% ID in 7 days, and 97% ID in 28 days with no signs of acute toxicity in the tissues studied under histological analysis. To our knowledge, this renal clearance is the best reported for Ag2Te NP, while being comparable to the highest renal clearance reported for any type of nanoparticle. Together, the results herein presented suggest the use of GSH-Ag2Te NPs as an X-ray contrast agent with the potential to be clinically translated in the future.

Silver telluride nanoparticles as biocompatible and enhanced contrast agents for X-ray imaging: an in vivo breast cancer screening study.

Silver sulfide nanoparticles (Ag2S NPs) have gained considerable interest in the biomedical field due to their photothermal ablation enhancement, near-infrared fluorescence properties, low toxicity levels, and multi-imaging capabilities. Silver telluride nanoparticles (Ag2Te NPs) have similar properties to Ag2S NPs, should also be stable due to an extremely low solubility product and should generate greater X-ray contrast since tellurium is significantly more attenuating than sulfur at diagnostic X-ray energies. Despite these attractive properties, Ag2Te NPs have only been studied in vivo once and at a low dose (2 mg Ag per kg). Herein, for the first time, Ag2Te NPs' properties and their application in the biomedical field were studied in vivo in the setting requiring the highest nanoparticle doses of all biomedical applications, i.e. X-ray imaging. Ag2Te NPs were shown to be stable, biocompatible (no acute toxicity observed in the cell lines studied or in vivo), and generated higher contrast, compared to controls, in the two X-ray imaging techniques studied: computed tomography (CT) and dual-energy mammography (DEM). In summary, this is the first study where Ag2Te NPs were explored in vivo at a high dose. Our findings suggest that Ag2Te NPs provide strong X-ray contrast while exhibiting excellent biocompatibility. These results highlight the potential use of Ag2Te NPs in the biomedical field and as X-ray contrast agents for breast cancer screening.

Labeling Stem Cells with a New Hybrid Bismuth/Carbon Nanotube Contrast Agent for X-Ray Imaging.

The poor retention and survival of cells after transplantation to solid tissue represent a major obstacle for the effectiveness of stem cell-based therapies. The ability to track stem cells in vivo can lead to a better understanding of the biodistribution of transplanted cells, in addition to improving the analysis of stem cell therapies' outcomes. Here, we described the use of a carbon nanotube-based contrast agent (CA) for X-ray computed tomography (CT) imaging as an intracellular CA to label bone marrow-derived mesenchymal stem cells (MSCs). Porcine MSCs were labeled without observed cytotoxicity. The CA consists of a hybrid material containing ultra-short single-walled carbon nanotubes (20–80 nm in length, US-tubes) and Bi(III) oxo-salicylate clusters which contain four Bi3+ ions per cluster (Bi4C). The CA is thus abbreviated as Bi4C@US-tubes.

Gentamicin-gold nanoparticles conjugate: a contrast agent for X-ray imaging of infectious foci due to Staphylococcus aureus.

There is no optimal imaging method for the detection of unknown infectious foci in some diseases. This study introduces a novel method in X-ray imaging of infection foci due to Staphylococcus aureus by developing a contrast agent based on gold nanoparticles (GNPs). GNPs in spherical shape were synthesised by the reduction of tetrachloroauric acid with sodium citrate. Then gentamicin was bound directly to citrate functionalised GNPs and the complex was stabilised by polyethylene glycol. The interaction of gentamicin with GNPs was confirmed by ultraviolet-visible and Fourier transform infrared spectroscopies. The stability of complex was studied in human blood up to 6 h. The stability of conjugate was found to be high in human blood with no aggregation. The biodistribution study showed localisation of gentamicin-GNPs conjugate at the site of Staphylococcal infection. The infection site was properly visualised in X-ray images in mouse model using the gentamicin-GNPs conjugate as a contrast agent. The results demonstrated that one may consider the potential of new nanodrug as a contrast agent for X-ray imaging of infection foci in human beings which needs more investigations.

Gold nanostars mediated combined photothermal and photodynamic therapy and X-ray imaging for cancer theranostic applications.

Gold nanomaterials possess unique physical and chemical properties, which attracted much attention in recent years. As a new type of gold nanomaterials, gold nanostars (GNSTs) have been prepared and characterized in this study. GNSTs under near-infrared (NIR) light irradiation can exert not only cancer photothermal therapy via heat production but also photodynamic therapy via generation of reactive oxygen species. GNSTs were able to enter the cytoplasm as well as nuclei of human breast michigan cancer foundation-7 (MCF-7) cells. Under NIR light irradiation, GNSTs caused more severe DNA damage, arrest the cell cycle in G0/G1 phase, and reduce more cellular glutathione level, causing more severe apoptosis and cell death in vitro. Intratumoral injection of GNSTs with NIR light irradiation significantly inhibited tumor growth in vivo. In addition, GNSTs were demonstrated to be a contrast agent for X-ray imaging. All the in vitro and in vivo results showed that GNSTs can be used for the potential diagnosis and medical treatment of cancer.

Radiopaque poly(ε-caprolactone) as additive for X-ray imaging of temporary implantable medical devices

A family of radiopaque PCL, poly(ε-caprolactone-co-α-triiodobenzoate-ε-caprolactone), has been designed, used and evaluated as macromolecular contrast agent for X-ray imaging of implantable polymeric biomaterials.

Biodistribution of X-ray iodinated contrast agent in nano-emulsions is controlled by the chemical nature of the oily core.

In this study, we investigated the role of the chemical nature of the oil droplet core of nano-emulsions used as contrast agents for X-ray imaging on their pharmacokinetics and biodistribution. To this end, we formulated PEGylated nano-emulsions with two iodinated oils (i.e., iodinated monoglyceride and iodinated castor oil) and compared them with another iodinated nano-emulsion based on iodinated vitamin E. By using dynamic light scattering and transmission electron microscopy, the three iodinated nano-emulsions were found to exhibit comparable morphologies, size, and surface composition. Furthermore, they were shown to be endowed with very high iodine concentration, which leads to stronger X-ray attenuation properties as compared to the commercial iodinated nano-emulsion Fenestra VC. The three nano-emulsions were i.v. administered in mice and monitored by microcomputed tomography (micro-CT). They showed high contrast enhancement in blood with similar half-life around 6 h but very different accumulation sites. While iodinated monoglycerides exhibited low accumulation in liver and spleen, high accumulation in spleen was observed for iodinated castor oil and in liver for vitamin E. These data clearly highlighted the important role of the oil composition of the nano-emulsion core to obtain strong X-ray contrast enhancement in specific targets such as liver, spleen, or only blood. These differences in biodistribution were partly attributed to differences in the uptake of the nanodroplets by the macrophages in vitro. Another key feature of these nano-emulsions is their long half-elimination time (several weeks), which offers sufficient retention for micro-CT imaging. This work paves the way for the design of nanoparticulate contrast agents for X-ray imaging of selected organs.

PEGylated Gold Nanoparticles as a Biocompatible Contrast Agent in X-ray Imaging of Breast Tumor in Mouse Model

Objective: Though biopsy is ultimately the gold standard for breast cancer detection, medical imaging can be a valuable tool for gathering information in vivo for both screening and diagnosis. In this study, we propose the use of gold nanoparticles (GNPs) modified with polyethylene glycol (PEG) as a biocompatible contrast agent in X- ray imaging of breast cancer in mouse model. . Methods: Gold nanoparticles in spherical shape were coated with PEG and the interaction was investigated by UV/vis spectroscopy. The UV/vis analysis was performed to check the stability of PEG-GNPs complex in human blood serum. The biodistribution and X–ray imaging studies were performed to evaluate the localization of PEGylated GNPs in xenografted breast tumor in mouse model. Results: The interaction of PEG with GNPs was confirmed by UV–vis spectroscopy. The stability of PEG-GNPs was found high at human blood serum with no aggregation. The biodistribution study showed the accumulation of PEGylated GNPs in the site of tumor. The tumor was properly visualized in X-ray images in mouse model. Conclusions: The results showed the potential of PEGylated gold nanoparticles as a contrast agent for X-ray imaging of breast cancer in humans that needs further investigations.

MULTIFUNCTIONAL FULLERENE- AND METALLOFULLERENE-BASED NANOBIOMATERIALS

Recent advances in nanotechnology have enabled the synthesis and characterization of nanomaterials suitable for applications in the field of biology and medicine. Due to their unique physico-chemical properties, carbon-based nanomaterials such as fullerenes, metallofullerenes, carbon nanotubes and graphene have been widely investigated as multifunctional materials for applications in tissue engineering, molecular imaging, therapeutics, drug delivery and biosensing. In this review, we focus on the multifunctional capabilities of fullerenes and metallofullerenes for diagnosis and therapy. Specifically, we review recent advances toward the development of fullerene- and metallofullerene-based magnetic resonance imaging (MRI) and X-ray imaging contrast agents, drug and gene delivery vehicles, and photodynamic therapy agents. We also discuss in vitro and in vivo toxicity, and biocompatibility issues associated with the use of fullerenes and metallofullerenes for biomedical applications.

Poly(ethylene glycol)-poly(ε-caprolactone) Iodinated Nanocapsules as Contrast Agents for X-ray Imaging

Synthesis and formulation of iodinated PCL-mPEG nanocapsules as new original blood pool contrast agents for computed tomography. PCL-mPEG was synthesized and formulated following the emulsion-solvent diffusion process, in the form of iodinated nanocapsules. Physico-chemical characterization of such nano-materials was performed by DLS and transmission electron microscopy. A stability study of the nanocapsules suspension was followed-up to 3 month. Blood biocompatibility was performed. Finally, the nanocapsules suspension radiopacity was evaluated in vitro then in vivo in mice as micro-CT contrast agent. In this study, the iodine concentration in nanocapsules suspension was about 70 mgI/mL. Besides, these nanocarriers appeared non-toxic, and stable in suspension. In vivo, i.v. administration of 10 μL/g of mouse body weight of theses nano-particles induced a vascular contrast enhancement of 168 HU and a half-life in blood of 4.2 +/- 0.5 h. Elimination route of these particles appears mainly performed by the liver, without sequestration in spleen and lymph nodes confirming their stealth properties. This study proposes the first example of iodinated biodegradable polymeric blood pool contrast agent, able to induce an exploitable contrast enhancement. The main advantage of polymeric system compared to lipid ones, lies in their stability and handling, e.g. towards drying for storage.

Gold nanoparticles as high-resolution X-ray imaging contrast agents for the analysis of tumor-related micro-vasculature

BackgroundAngiogenesis is widely investigated in conjunction with cancer development, in particular because of the possibility of early stage detection and of new therapeutic strategies. However, such studies are negatively affected by the limitations of imaging techniques in the detection of microscopic blood vessels (diameter 3-5 μm) grown under angiogenic stress. We report that synchrotron-based X-ray imaging techniques with very high spatial resolution can overcome this obstacle, provided that suitable contrast agents are used.ResultsWe tested different contrast agents based on gold nanoparticles (AuNPs) for the detection of cancer-related angiogenesis by synchrotron microradiology, microtomography and high resolution X-ray microscopy. Among them only bare-AuNPs in conjunction with heparin injection provided sufficient contrast to allow in vivo detection of small capillary species (the smallest measured lumen diameters were 3-5 μm). The detected vessel density was 3-7 times higher than with other nanoparticles. We also found that bare-AuNPs with heparin allows detecting symptoms of local extravascular nanoparticle diffusion in tumor areas where capillary leakage appeared.ConclusionsAlthough high-Z AuNPs are natural candidates as radiology contrast agents, their success is not guaranteed, in particular when targeting very small blood vessels in tumor-related angiography. We found that AuNPs injected with heparin produced the contrast level needed to reveal--for the first time by X-ray imaging--tumor microvessels with 3-5 μm diameter as well as extravascular diffusion due to basal membrane defenestration. These results open the interesting possibility of functional imaging of the tumor microvasculature, of its development and organization, as well as of the effects of anti-angiogenic drugs.

Highly-Iodinated Fullerene as a Contrast Agent For X-ray Imaging

The first fullerene-based X-ray contrast agent (CA) has been designed, synthesized, and characterized. The new CA is an externally functionalized derivative of C 60 that is conceptually based on contemporary X-ray CA, all of which use iodine as the X-ray attenuating vehicle and are based on the 2,4,6-triiodinated-benzene-ring substructure. Using a modified Bingel-type reaction, a single addend containing 6 iodine atoms and 8 protected hydroxyl groups was appended to C 60 followed by the addition of 4 more addends each containing 4 protected hydroxyl groups. Final deprotection afforded the highly water-soluble (>460 mg/mL), non-ionic, highly-iodinated (24% I) fullerene for application as an X-ray contrast agent.

Niosomes as carriers of radiopaque contrast agents for X-ray imaging

Non-ionic surfactant vesicles (niosomes) are considered as carriers of iobitridol, a diagnostic agent used for X-ray imaging. The niosomes, with a diameter between 150 and 175 nm, are prepared using the film-hydration method followed by sonication. These vesicles were obtained with appropriate mixtures of D-alpha tocopheryl polyethylene glycol 1000 succinate, polyoxyethylene glycol 4000 stearate, sorbitan monostearate, cholesterol and dicetylphosphate. Methods allowing the increase of the rate of encapsulation and the stability of the vesicles were carried out. In addition to the study of the formulation of the vesicles, the physico-chemical and morphological properties of the vesicles have been studied.

Starch microspheres as carriers for X-ray imaging contrast agents: Synthesis and stability of new amino-acid linker derivatives

The relative stability of particulate contrast agents for X-ray imaging, consisting of a succinic-acid derivative of a water-soluble X-ray contrast agent bound to starch particles through an amino-acid ester bond, has been studied. To investigate the effect of chain length of the amino-acid linker on degradation rate, two glycine-linked derivatives and a corresponding β-alanine-linked derivative were prepared as model compounds. The cleavage rate of the amino-acid ester bond in the starch particle β-alanine derivative had a significantly lower cleavage rate than in the corresponding glycine derivatives; after 22 h in human blood serum at 37 °C the remaining fraction of the undegraded β-alanine-linked derivative was 78%, while 31.1 and 29.3% were the remaining fractions of the two glycine-linked derivatives. The cleavage data correlated well with biphasic cleavage processes with two distinct half lives for the respective pseudo first order processes. The second preparation with the glycine linker had a cleavage profile and rate equivalent to that of the first one in human blood serum, but the corresponding hydrolysis in phosphate buffer was significantly slower with 79.9%-remaining fraction after 22 h, and was apparently a monophasic pseudo first order reaction. Variation of the degradability of the starch matrix had apparently no significant effect on the cleavage rates of the linker. This suggests that components in the human blood serum catalyze the cleavage of the ester bond in these derivatives and that a fraction of the covalently bound contrast agent had a significantly slower cleavage rate from the matrix. The derivative with a glycine linker between the carrier matrix and the contrast agent is a promising candidate for liver and spleen directed X-ray contrast with respect to density of contrast generating iodine and biodegradability.