In vivo visualization of gold-loaded cells in mice using x-ray computed tomography

Astolfo, Alberto; Schültke, Elisabeth; Menk, R.H.; Kirch, Robert D.; Juurlink, Bernhard H.J.; Hall, Christopher; Harsan, Laura‐Adela; Stebel, Marco; Barbetta, Davide; Tromba, Giuliana; Arfelli, Fulvia

doi:10.1016/j.nano.2012.06.004

Cited by 58 publications

(57 citation statements)

References 30 publications

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“…There are occasional reports on using other particles, e.g. gold nanoparticles for CT imaging (74), manganese particles for MR imaging (75) or positron labeled particles for PET imaging as in the case of 64 Co-labeled chitosan nanoparticles (76) but the most widely used particles have been either gadolinium (paramagnetic) or iron oxide (superparamagnetic) nanoparticles for MR imaging (65). A weakness of using standard paramagnetic agents is that they do not cause a change in MR signal that is large enough to allow visualization of relatively small numbers of cells.…”

Section: Nanoparticles As Diagnostic Probesmentioning

confidence: 99%

Nanoparticles for Imaging: Top or Flop?

Kießling¹,

Mertens²,

Grimm³

et al. 2014

Radiology

193

146

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Nanoparticles are frequently suggested as diagnostic agents. However, except for iron oxide nanoparticles, diagnostic nanoparticles have been barely incorporated into clinical use so far. This is predominantly due to difficulties in achieving acceptable pharmacokinetic properties and reproducible particle uniformity as well as to concerns about toxicity, biodegradation, and elimination. Reasonable indications for the clinical utilization of nanoparticles should consider their biologic behavior. For example, many nanoparticles are taken up by macrophages and accumulate in macrophage-rich tissues. Thus, they can be used to provide contrast in liver, spleen, lymph nodes, and inflammatory lesions (eg, atherosclerotic plaques). Furthermore, cells can be efficiently labeled with nanoparticles, enabling the localization of implanted (stem) cells and tissue-engineered grafts as well as in vivo migration studies of cells. The potential of using nanoparticles for molecular imaging is compromised because their pharmacokinetic properties are difficult to control. Ideal targets for nanoparticles are localized on the endothelial luminal surface, whereas targeted nanoparticle delivery to extravascular structures is often limited and difficult to separate from an underlying enhanced permeability and retention (EPR) effect. The majority of clinically used nanoparticle-based drug delivery systems are based on the EPR effect, and, for their more personalized use, imaging markers can be incorporated to monitor biodistribution, target site accumulation, drug release, and treatment efficacy. In conclusion, although nanoparticles are not always the right choice for molecular imaging (because smaller or larger molecules might provide more specific information), there are other diagnostic and theranostic applications for which nanoparticles hold substantial clinical potential.

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Section: Nanoparticles As Diagnostic Probesmentioning

confidence: 99%

Nanoparticles for Imaging: Top or Flop?

Kießling¹,

Mertens²,

Grimm³

et al. 2014

Radiology

193

146

View full text Add to dashboard Cite

show abstract

“…Astolfo et al and Menk et al performed detailed analysis of gold nanoparticle uptake in cells, as well in vivo detection and proliferation of gold labeled tumor cells in rat brain tumor models. 13–14 Moreover, recent studies utilizing synchrotron radiation sources for x-rays, have been able image gold nanoparticle labeled cells with single cell resolution in ex vivo and in vitro samples. 15–16 Of the few studies regarding monocyte tracking, SPECT and MRI modalities were used.…”

Section: Introductionmentioning

confidence: 99%

Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography

et al. 2016

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Monocytes are actively recruited from the circulation into developing atherosclerotic plaques. In the plaque, monocytes differentiate into macrophages and eventually form foam cells. Continued accumulation of foam cells can lead to plaque rupture and subsequent myocardial infarction. X-ray computed tomography (CT) is the best modality to image the coronary arteries non-invasively, therefore we have sought to track the accumulation of monocytes into atherosclerotic plaques using CT. Gold nanoparticles were synthesized and stabilized with a variety of ligands. Select formulations were incubated with an immortalized monocyte cell line in vitro and evaluated for cytotoxicity, effects on cytokine release, and cell uptake. These data identified a lead formulation, 11-MUDA capped gold nanoparticles, to test for labeling primary monocytes. The formulation did not the affect the viability or cytokine release of primary monocytes and was highly taken up by these cells. Gold labeled primary monocytes were injected into apolipoprotein E deficient mice kept on Western diet for 10 weeks. Imaging was done with a microCT scanner. A significant increase in attenuation was measured in the aorta of mice receiving the gold labeled cells as compared to control animals. Following the experiment, the biodistribution of gold was evaluated in major organs. Additionally, plaques were sectioned and examined with electron microscopy. The results showed that gold nanoparticles were present inside monocytes located within plaques. This study demonstrates the feasibility of using gold nanoparticles as effective cell labeling contrast agents for non-invasive imaging of monocyte accumulation within plaques with CT.

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“…6,[27][28][29][30][31] Nevertheless, uptake and biocompatibility of several GNPs are controversially discussed. Some studies declare them as nontoxic, 32 but some see their toxic potential 33 to depend on size, surface chemistry, and shape of the GNPs.…”

mentioning

confidence: 99%

Gold nanoparticles allow detection of early-stage edema in mice via computed tomography imaging

Domey¹,

Teichgräber²,

Hilger³

2015

IJN

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Due to their high X-ray attenuation, gold nanoparticles (GNPs) emerged as preclinical contrast agents by giving high vasculature contrast. For this reason, GNPs are regularly applied for computed tomography (CT) imaging of tumors but not for the visualization of inflammation. The aim of this study was to evaluate the biocompatibility and applicability of preclinical GNPs (AuroVist™) of two different sizes (1.9 nm and 15 nm) for the detection of inflammation-associated phagocytes in early-stage edema. Both GNP variants were stable under in vitro conditions and achieved high micro-CT (mCT) contrast after embedment into agarose. Fifteen-nanometer GNPs were detected after uptake into macrophages via mCT imaging exhibiting higher X-ray contrast than cells treated with 1.9 nm GNPs and untreated ones. Both 1.9 nm and 15 nm GNPs exhibited good biocompatibility on murine macrophages according to ATP and cellular dehydrogenase levels. Reactive oxygen species levels produced by phagocytic cells decreased significantly ( P ≤0.05) after co-incubation with GNPs regardless of the size of the nanoparticle (NP) in comparison to untreated control cells. In vivo mCT studies of inflammation imaging revealed that GNPs with a diameter of 15 nm accumulated within subcutaneous edema 2 hours after injection with a maximum signaling 8 hours postinjection and could be detected up to 48 hours within the edema region. In contrast, 1.9 nm GNPs were not shown to accumulate at the site of the inflammation region and were mostly excreted via the renal system 2–4 hours after injection. In conclusion, our study demonstrated that both GNP variants (1.9 nm and 15 nm) were stable and biocompatible under in vitro conditions. However, only 15 nm NPs have the potential as contrast agent for phagocyte labeling and applications in CT imaging of inflammation on a cellular level.

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In vivo visualization of gold-loaded cells in mice using x-ray computed tomography

Cited by 58 publications

References 30 publications

Nanoparticles for Imaging: Top or Flop?

Nanoparticles for Imaging: Top or Flop?

Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography

Gold nanoparticles allow detection of early-stage edema in mice via computed tomography imaging

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