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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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Au3Cu1 Nanoparticles

Au3Cu1-NPs
, PhD
National Center for Biotechnology Information, NLM, NIH, vog.hin.mln.ibcn@dacim

Created: ; Last Update: August 18, 2008.

Chemical name:Au3Cu1 Nanoparticles
Abbreviated name:Au3Cu1-NPs
Synonym:
Agent Category:Metal
Target:Non-targeted
Target Category:Blood-pool retention
Method of detection:MRI
Source of signal\contrast:Cu
Activation:No
Studies:
  • Checkbox In vitro
  • Checkbox Rodents
No structure is available in PubChem.

Background

[PubMed]

Magnetic resonance imaging (MRI) maps information about tissues spatially and functionally. Protons (hydrogen nuclei) are widely used in MRI because of their abundance in water molecules. Water comprises ~80% of most soft tissue. The contrast of proton MRI depends largely on the density of the nucleus (proton spins), the relaxation times of the nuclear magnetization (T1, longitudinal, and T2, transverse), the magnetic environment of the tissues, and the blood flow to the tissues. Insufficient contrast between normal and diseased tissues requires the development of contrast agents. Most contrast agents affect the T1 and T2 relaxation times of the surrounding nuclei, mainly the protons of water. T2* is the spin–spin relaxation time composed of variations from molecular interactions and intrinsic magnetic heterogeneities of tissues in the magnetic field (1). Cross-linked iron oxide nanoparticles and other iron oxide formulations primarily affect T2 and lead to decreased signals. On the other hand, paramagnetic T1 agents such as gadolinium (Gd3+) and manganese (Mn2+) accelerate T1 relaxation and lead to brighter contrast images (2).

Gold nanoparticles have been used as X-ray and optical contrast agents in small animals with little toxicity (3). Su et al. (4) have developed hollow Au3Cu1 nanoparticles (nanoshells and nanocapsules) as bimetallic MRI contrast agents with enhancing effects in T1- and T2-weighted imaging. A Cu3+ ion has an electron configuration of d8 with two unpaired electrons and less magnetic moment than Gd3+, with seven unpaired electrons; however, hollow Au3Cu1 nanoparticles are made of large numbers of paramagnetic Cu3+ ions to provide a superparamagnetic effect. The large surface area of the porous nanoparticles also provides an effective interaction of Cu3+ ions with water molecules.

Synthesis

[PubMed]

Su et al. (4) produced Au3Cu1 nanoparticles by adding 1 × 10-6 mol HAuCl4 (dehydrated) to a Cu-colloidal solution, which was prepared with laser irradiation of CuO in 2-propanol. The mixture was sonicated for 10 min to form hollow Au3Cu1 nanoshells. The Au3Cu1 nanoshells were coated with polyelectrolyte polyethylenimine (PEI) and poly(acrylic acid) (PAA) polymers to form Au3Cu1 nanocapsules. The nanoshell cores were 48.9 ± 19.1 nm in diameter, and the shells were 5.8 ± 1.8 nm thick as determined with transmission electron microscopy. The pores were 1–2 nm in diameter. The nanocapsule shells were 6.1 ± 1.2 nm thick. The number of copper atoms/nanoparticle was estimated to be 4.98 × 105.

In Vitro Studies: Testing in Cells and Tissues

[PubMed]

For in vitro MR images as well as both T1 and T2 measurements at 3 T, all nanoshells and nanocapsules were dispersed in 5% agarose gel at various concentrations (0.125, 0.25, 1.25, 2.5, and 5 mg/ml) (4). Adding Au3Cu1 nanocapsules to the agarose gel brightened the T1 image and enhanced the T1-1 (longitudinal relaxation rate) of water protons. The T1-weighted MR signal intensity increased up to ~89% as the Au3Cu1 nanocapsule concentrations increased from 0 to 5.00 mg/mL; however, use of Au3Cu1 nanoshells resulted in only ~26% increase in T1 image intensity. Interestingly, both nanoparticles enhanced T2-weighted image intensity by 8% to 11% at 0.125 mg/ml and decreased by 6% and 76% at 5 mg/ml for nanoshells and nanocapsules, respectively. The proton r1 relaxivities were as large as 3.0 × 104 mM-1s-1 (Au3Cu1 nanocapsules) and 2.3 × 104 mM-1s-1 (Au3Cu1 nanoshells). The proton r2 relaxivities were 2.39 × 105 mM-1s-1 for Au3Cu1 nanocapsules and 1.82 × 106 mM-1s-1 for Au3Cu1 nanoshells. Both exhibited little cytotoxicity to monkey kidney epithelial Vero cells in culture at concentrations of 0.1–10,000 ng/ml at 37°C up to 24 h.

Animal Studies

Rodents

[PubMed]

Su et al. (4) studied the long-term toxicological effects in normal mice (n = 6 mice/group) at 30 days after intravenous injection of 2, 20, and 40 mg/kg Au3Cu1 nanocapsules with viability rates of 100%, 83%, and 67%, respectively. Most of the Au and Cu were found in the urine at 3 h after injection. MRI studies (T1- and T2-weighted imaging at 3 T) were performed in normal mice after injection of 20 mg/kg Au3Cu1 nanocapsules. Both images were enhanced in the heart and major vessels at 2 h after injection. Images of the blood vessels in the liver were also enhanced. The calculated blood concentration is ~0.25mg/ml after injection of 20 mg/kg. Au3Cu1 nanocapsules may be a tool as positive contrast agent for use in MR angiography.

Other Non-Primate Mammals

[PubMed]

No publication is currently available.

Non-Human Primates

[PubMed]

No publication is currently available.

Human Studies

[PubMed]

No publication is currently available.

References

1.
Wang Y.X. , Hussain S.M. , Krestin G.P. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol. 2001;11(11):2319–31. [PubMed: 11702180]
2.
Kabalka G. , Buonocore E. , Hubner K. , Moss T. , Norley N. , Huang L. Gadolinium-labeled liposomes: targeted MR contrast agents for the liver and spleen. Radiology. 1987;163(1):255–8. [PubMed: 3454163]
3.
Hainfeld J.F. , Slatkin D.N. , Focella T.M. , Smilowitz H.M. Gold nanoparticles: a new X-ray contrast agent. Br J Radiol. 2006;79(939):248–53. [PubMed: 16498039]
4.
Su C.H. , Sheu H.S. , Lin C.Y. , Huang C.C. , Lo Y.W. , Pu Y.C. , Weng J.C. , Shieh D.B. , Chen J.H. , Yeh C.S. Nanoshell magnetic resonance imaging contrast agents. J Am Chem Soc. 2007;129(7):2139–46. [PubMed: 17263533]

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