An x-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles. Nat Mater

Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Nature Material (Impact Factor: 36.5). 02/2006; 5(2):118-22. DOI: 10.1038/nmat1571
Source: PubMed


Nanomaterials have become increasingly important in the development of new molecular probes for in vivo imaging, both experimentally and clinically. Nanoparticulate imaging probes have included semiconductor quantum dots, magnetic and magnetofluorescent nanoparticles, gold nanoparticles and nanoshells, among others. However, the use of nanomaterials for one of the most common imaging techniques, computed tomography (CT), has remained unexplored. Current CT contrast agents are based on small iodinated molecules. They are effective in absorbing X-rays, but non-specific distribution and rapid pharmacokinetics have rather limited their microvascular and targeting performance. Here we propose the use of a polymer-coated Bi(2)S(3) nanoparticle preparation as an injectable CT imaging agent. This preparation demonstrates excellent stability at high concentrations (0.25 M Bi(3+)), high X-ray absorption (fivefold better than iodine), very long circulation times (>2 h) in vivo and an efficacy/safety profile comparable to or better than iodinated imaging agents. We show the utility of these polymer-coated Bi(2)S(3) nanoparticles for enhanced in vivo imaging of the vasculature, the liver and lymph nodes in mice. These nanoparticles and their bioconjugates are expected to become an important adjunct to in vivo imaging of molecular targets and pathological conditions.

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Available from: Jan Grimm, Sep 26, 2014
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    • "Several nanoparticulated CT contrast agents have been reported based on iodine functionalized polymers [3], gold nanoparticles [4], core–shell iron oxide/tantalum oxide nanoparticles [5] and iron-platinum alloy nanoparticles [6]. Nanoparticulated CT contrasts bearing bismuth, in particular bismuth sulphide nanodots (2–3 nm) [8] [9] [10] [11], have obtained special attention due to a combination of low price, low toxicity and a high x-ray attenuation coefficient [2] [7]. This material has been successfully prepared in large quantities and targeted to contrast breast cancer [10]. "
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    ABSTRACT: Many therapeutic applications of magnetic nanoparticles involve the local administration of nanometric iron oxide based materials as seeds for magnetothermia or drug carriers. A simple and widespread way of controlling the process using x-ray computed tomography (CT) scanners is desirable. The combination of iron and bismuth in one entity will increase the atenuation of x-rays, offering such a possibility. In order to check this possibility core-shell nanocrystals of iron oxide@bismuth oxide have been synthesized by an aqueous route and stabilized in water by polyethylene glycol (PEG), and we have evaluated their ability to generate contrast by CT and magnetic resonance imaging (MRI) to measure the radiopacity and proton relaxivities using phantoms. High-resolution scanning transmission electron microscopy (STEM) revealed that the material consists of a highly crystalline 8 nm core of maghemite and a 1 nm shell of bismuth atoms either isolated or clustered on the nanocrystal's surface. The comparison of μCT and MRI images of mice acquired in the presence of the contrast shows that when local accumulations of the magnetic nanoparticles take place, CT images are more superior in the localization of the magnetic nanoparticles than MRI images, which results in magnetic field inhomogeneity artifacts.
    Nanotechnology 03/2015; 26(13):135101. DOI:10.1088/0957-4484/26/13/135101 · 3.82 Impact Factor
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    • "However, to develop AuNP-based CT contrast agents with desirable properties, such as good biocompatibility, easy and controllable surface modification, sharp contrast, and prolonged imaging time [23-25], multiple complicated steps are generally required. Recent studies have shown that proper modification of AuNPs can extend their circulation time in cardiovascular diseases by decreasing the rapid uptake and clearance by the reticuloendothelial system (RES) [19,26-28]. One promising and efficient technique to achieve this goal is to modify AuNPs with polyethylene glycol (PEG) molecules [29,30]. "
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    ABSTRACT: We report a new use of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with good biocompatibility for in vitro and in vivo imaging of atherosclerotic mice by computed tomography (CT). In this study, Au DENPs were synthesized using poly(amidoamine) (PAMAM) dendrimers of generation 5 (G5.NH2) modified by PEG monomethyl ether (G5.NH2-mPEG20) as templates. In vitro cytotoxicity and flow cytometry assays show that the formed PEGylated Au DENPs have good biocompatibility and are non-cytotoxic at the Au concentration up to 300 μM. Silver staining and transmission electron microscopy (TEM) further confirm that the Au DENPs are able to be uptaken by macrophages and are located dominantly in the lysosomes of the cells. Importantly, the formed PEGylated Au DENPs are able to be used for CT imaging of murine macrophages in vitro and macrophages in atherosclerotic mice in vivo using apolipoprotein-E-gene-deficient mice as a model. These findings suggest that the formed PEGylated Au DENPs are a promising contrast agent for CT imaging of atherosclerosis.
    Nanoscale Research Letters 09/2014; 9(1):529. DOI:10.1186/1556-276X-9-529 · 2.78 Impact Factor
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    • ". 3. Blood pool contrast agents: a prerequisite for targeted imaging As discussed in the Introduction section, the clinically water-soluble contrast agents are not compatible with micro-CT applications, hence the necessity to develop surface-controlled NPs containing high Z-number atoms [21] [22] [23] [24] [25] "
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    ABSTRACT: Micro-computed tomography (micro-CT) is an X-ray based instrument that it is specifically designed for biomedical research at a preclinical stage for live imaging of small animals. This imaging modality is cost-effective, fast, and produces remarkable high-resolution images of X-ray opaque skeleton. Administration of biocompatible X-ray opaque contrast agent allows delineation of the blood vessels, and internal organs and even detection of tumor metastases as small as 300 mu m. However, the main limitation of micro-CT lies in the poor efficacy or toxicity of the contrast agents. Moreover, contrast agents for micro-CT have to be stealth nanoparticulate systems, i.e. preventing their rapid renal clearance. The chemical composition and physicochemical properties will condition their uptake and elimination pathways, and therefore all the biological fluids, organs, and tissues trough this elimination route of the nanoparticles will be contrasted. Furthermore, several technologies playing on the nanoparticle properties, aim to influence these biological pathways in order to induce their accumulation onto given targeted sites, organs of tumors. In function of the methodologies carried out, taking benefit or not of the action of immune system, of the natural response of the organism like hepatocyte uptake or enhanced permeation and retention effect, or even accumulation due to ligand/receptor interactions, the technologies are called passive or active targeted imaging. The present review presents the most recent advances in the development of specific contrast agents for targeted X-ray imaging micro-CT, discussing the recent advance of in vivo targeting of nanoparticulate contrast agents, and the influence of the formulations, nature of the nanocarrier, nature and concentration of the X-ray contrasting materials, effect of the surface properties, functionalization and bioconjugation. The pharmacokinetic and versatility of nanometric systems appear particularly advantageous for addressing the versatile biomedical research needs. State of the art investigations are on going to propose contrast agents with tumor accumulating properties and will contribute for development of safer cancer medicine having detection and therapeutic modalities.
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