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Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents.

Estelrich J, Sánchez-Martín MJ, Busquets MA - Int J Nanomedicine (2015)

Bottom Line: Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements.They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively.Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents.

View Article: PubMed Central - PubMed

Affiliation: Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Catalonia, Spain ; Institut de Nanociència I Nanotecnologia (IN UB), Barcelona, Catalonia, Spain.

ABSTRACT
Magnetic resonance imaging (MRI) has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times (T 1, spin-lattice relaxation and T 2, spin-spin relaxation) of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents) are administered prior to the scanning. Shortening T 1 and T 2 increases the corresponding relaxation rates, 1/T 1 and 1/T 2, producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T 2-weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions), providing positive contrast in T 1-weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor) targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively. Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration of the coupling of cRGD peptide to the SPIONs.Notes: (A) MRI cross-section image of the U87MG tumors implanted in mice; (B) without the nanoparticles; and (C) with the injection of 300 μg of cRGD-SPIONs. Reprinted with permission from Ho D, Sun X, Sun S. Monodisperse magnetic nanoparticles for thera nostic applications. Acc Chem Res. 2011;44:875–882.60 Copyright 2011 American Chemical Society.Abbreviations: cRGD, cyclic arginine-glycine-aspartic acid; SPIONs, superparamagnetic iron oxide nanoparticles; MRI, magnetic resonance imaging.
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f2-ijn-10-1727: Schematic illustration of the coupling of cRGD peptide to the SPIONs.Notes: (A) MRI cross-section image of the U87MG tumors implanted in mice; (B) without the nanoparticles; and (C) with the injection of 300 μg of cRGD-SPIONs. Reprinted with permission from Ho D, Sun X, Sun S. Monodisperse magnetic nanoparticles for thera nostic applications. Acc Chem Res. 2011;44:875–882.60 Copyright 2011 American Chemical Society.Abbreviations: cRGD, cyclic arginine-glycine-aspartic acid; SPIONs, superparamagnetic iron oxide nanoparticles; MRI, magnetic resonance imaging.

Mentions: Iron oxide nanoparticles require specific approaches to target cells other than macrophages. Since biochemical epitopes of interest are often present in nanomolar or picomolar concentrations, particle relaxivities of around 1,000,000 mM−1·s−1 are required to achieve acceptable contrast-to-noise ratios at the typical field strength.48 In this way, contrast agents that target specific tissue can increase the sensitivity by increasing the local SPION concentration. To achieve such sensitivity in the nanomolar range, the surface of the SPIONs may be modified by active targeting strategies, such as the addition of ligands that are recognized by molecular signatures of afflicted cells. Polyethyleneimine (PEI) is one of the more used ligands.49 The same group50,51 has reported that hyaluronic acid targeted iron oxide nanoparticles are efficient probes for targeted MRI of cancer cells in vitro and xenografted tumor model in vivo. Other types of ligands have been studied for the targeting of such markers including antibodies, small peptides, lectins, aptamers, engineered proteins, and protein fragments.52 For instance, USPIONs of less than 10 nm in hydrodynamic diameter were tested for tumor-specific MRI targeting. In that study, the USPIONs were stabilized by 4-methylcatechol, and a cyclic arginine–glycine–aspartic acid (cRGD) peptide was coupled via the Mannich reaction53 (Figure 2).


Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents.

Estelrich J, Sánchez-Martín MJ, Busquets MA - Int J Nanomedicine (2015)

Schematic illustration of the coupling of cRGD peptide to the SPIONs.Notes: (A) MRI cross-section image of the U87MG tumors implanted in mice; (B) without the nanoparticles; and (C) with the injection of 300 μg of cRGD-SPIONs. Reprinted with permission from Ho D, Sun X, Sun S. Monodisperse magnetic nanoparticles for thera nostic applications. Acc Chem Res. 2011;44:875–882.60 Copyright 2011 American Chemical Society.Abbreviations: cRGD, cyclic arginine-glycine-aspartic acid; SPIONs, superparamagnetic iron oxide nanoparticles; MRI, magnetic resonance imaging.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358688&req=5

f2-ijn-10-1727: Schematic illustration of the coupling of cRGD peptide to the SPIONs.Notes: (A) MRI cross-section image of the U87MG tumors implanted in mice; (B) without the nanoparticles; and (C) with the injection of 300 μg of cRGD-SPIONs. Reprinted with permission from Ho D, Sun X, Sun S. Monodisperse magnetic nanoparticles for thera nostic applications. Acc Chem Res. 2011;44:875–882.60 Copyright 2011 American Chemical Society.Abbreviations: cRGD, cyclic arginine-glycine-aspartic acid; SPIONs, superparamagnetic iron oxide nanoparticles; MRI, magnetic resonance imaging.
Mentions: Iron oxide nanoparticles require specific approaches to target cells other than macrophages. Since biochemical epitopes of interest are often present in nanomolar or picomolar concentrations, particle relaxivities of around 1,000,000 mM−1·s−1 are required to achieve acceptable contrast-to-noise ratios at the typical field strength.48 In this way, contrast agents that target specific tissue can increase the sensitivity by increasing the local SPION concentration. To achieve such sensitivity in the nanomolar range, the surface of the SPIONs may be modified by active targeting strategies, such as the addition of ligands that are recognized by molecular signatures of afflicted cells. Polyethyleneimine (PEI) is one of the more used ligands.49 The same group50,51 has reported that hyaluronic acid targeted iron oxide nanoparticles are efficient probes for targeted MRI of cancer cells in vitro and xenografted tumor model in vivo. Other types of ligands have been studied for the targeting of such markers including antibodies, small peptides, lectins, aptamers, engineered proteins, and protein fragments.52 For instance, USPIONs of less than 10 nm in hydrodynamic diameter were tested for tumor-specific MRI targeting. In that study, the USPIONs were stabilized by 4-methylcatechol, and a cyclic arginine–glycine–aspartic acid (cRGD) peptide was coupled via the Mannich reaction53 (Figure 2).

Bottom Line: Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements.They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively.Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents.

View Article: PubMed Central - PubMed

Affiliation: Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Catalonia, Spain ; Institut de Nanociència I Nanotecnologia (IN UB), Barcelona, Catalonia, Spain.

ABSTRACT
Magnetic resonance imaging (MRI) has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times (T 1, spin-lattice relaxation and T 2, spin-spin relaxation) of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents) are administered prior to the scanning. Shortening T 1 and T 2 increases the corresponding relaxation rates, 1/T 1 and 1/T 2, producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T 2-weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions), providing positive contrast in T 1-weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor) targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively. Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents.

No MeSH data available.


Related in: MedlinePlus