Magnetic resonance imaging at 1.5 T with immunospecific contrast agent in vitro and in vivo in a xenotransplant model

Baio, Gabriella; Fabbi, Marina; Totero, Daniela de; Ferrini, Silvano; Cilli, Michele; Derchi, Lorenzo E.; Neumaier, Carlo Emanuele

doi:10.1007/s10334-006-0059-6

Cited by 15 publications

(20 citation statements)

References 13 publications

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“…When reaching r 2 /r 1 close to unity, brightening is observed and can be clearly shown in T 1 -weighted images [4,5]. Adequately capped with biocompatible molecules, fine USPIOs can therefore provide positive contrast (T 1 ) and high signal intensities, which can be valuable assets for vascular imaging [5][6][7], cell tracking [8]and also molecular targeting studies [9]. The signal intensity on T 1 -weighted images of contrast agent solutions obtained by spinecho MR sequences can be estimated by using both r 1 (1/ T 1 ) and r 2 (1/ T 2 ), according to the following equation [10]:…”

Section: Introductionmentioning

confidence: 99%

Polyethylene glycol-covered ultra-small Gd₂O₃nanoparticles for positive contrast at 1.5 T magnetic resonance clinical scanning

et al. 2007

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The size distribution and magnetic properties of ultra-small gadolinium oxide crystals (US-Gd 2 O 3 ) were studied, and the impact of polyethylene glycol capping on the relaxivity constants (r 1 , r 2 ) and signal intensity with this contrast agent was investigated. Size distribution and magnetic properties of US-Gd 2 O 3 nanocrystals were measured with a TEM and PPMS magnetometer. For relaxation studies, diethylene glycol (DEG)-capped US-Gd 2 O 3 nanocrystals were reacted with PEG-silane (MW 5000). Suspensions were adequately dialyzed in water to eliminate traces of Gd 3+ and surfactants. The particle hydrodynamic radius was measured with dynamic light scattering (DLS) and the proton relaxation times were measured with a 1.5 T MRI scanner. Parallel studies were performed with DEG-Gd 2 O 3 and PEG-silane-SPGO (Gd 2 O 3 , < 40 nm diameter). The small and narrow size distribution of US-Gd 2 O 3 was confirmed with TEM (∼3nm)andDLS.PEG-silane-US-Gd 2 O 3 relaxation parameters were twice as high as for Gd-DTPA and the r 2 /r 1 ratio was 1.4. PEG-silane-SPGO gave low r 1 relaxivities and high r 2 /r 1 ratios, less compatible with positive contrast agent requirements. Higher r 1 were obtained with PEG-silane in comparison to DEG-Gd 2 O 3 . Treatment of DEG-US-Gd 2 O 3 with PEG-silane provides enhanced relaxivity while preventing aggregation of the oxide cores. This study confirms that PEG-covered Gd 2 O 3 nanoparticles can be used for positively contrasted MR applications requiring stability, biocompatible coatings and nanocrystal functionalization.

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Section: Introductionmentioning

confidence: 99%

Polyethylene glycol-covered ultra-small Gd₂O₃nanoparticles for positive contrast at 1.5 T magnetic resonance clinical scanning

et al. 2007

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“…Similar to other studies for antibody-functionalized iron nanoparticles, our data suggested that the novel USPIO-CD133 Ab could differentially bind and have the potential to serve as a targeted contrast agent in CSC detection and monitoring by MRI ( Figure 5). [24][25][26][27]53 Consistent with the study regarding to in vivo detection of c-Met expression in rat hepatocarcinogenesis model, intravenous injection of USPIO-CD133 Ab successfully targets and labels the tumor cells in rat tumor models. 58 Studies have shown that polymer-coated nanoparticles, such as USPIO used in the present study, have no or minimal impact on cell viability, proliferation, ROS formation, apoptosis rate, and function, and that they have low toxicity in the majority of cells studied.…”

mentioning

confidence: 84%

“…Precise targeting is based on the use of specific ligands (antibodies, peptides, polysaccharides, and drugs), and this approach can be used in the design of ligand-directed, site-specific contrast accumulating agents and other targeted therapies. [23][24][25][26][27][28][29] By labeling CSCs with SPIO/USPIO, the CSC can be identified and tracked in vivo using an MRI scanner, a reliable anatomical and functional assessment of tumor-bearing animals. 30 With the help of SPIO/USPIO-labeling techniques, more studies identifying and characterizing CSCs as well as developing therapeutic treatments can be accomplished.…”

mentioning

confidence: 99%

“…17,24,[26][27][28][48][49][50] In this study, USPIO was conjugated with antibodies for the recognition of CD133, a surface marker associated with colorectal cancer and brain tumors, among other cancers, to produce a novel targeted contrast agent for detecting CSCs in vivo. Observed from transmission electron microscopy, the mean core diameter of whole particles was 29±7.9 nm, which assured efficient targeting and optical imaging of tumors in vitro and in vivo (Figure 1).…”

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confidence: 99%

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Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging

Chen¹,

Liou²,

Pan³

et al. 2015

IJN

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Background The use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to visualize cells has been applied clinically, showing the potential for monitoring cells in vivo with magnetic resonance imaging (MRI). USPIO conjugated with anti-CD133 antibodies (USPIO-CD133 Ab) that recognize the CD133 molecule, a cancer stem cell marker in a variety of cancers, was studied as a novel and potent agent for MRI contrast enhancement of tumor cells. Materials and methods Anti-CD133 antibodies were used to conjugate with USPIO via interaction of streptavidin and biotin for in vivo labeling of CD133-positive cells in xenografted tumors and N -ethyl- N -nitrosourea (ENU)-induced brain tumors. The specific binding of USPIO-CD133 Ab to CD133-positive tumor cells was subsequently detected by Prussian blue staining and MRI with T2-weighted, gradient echo and multiple echo recombined gradient echo images. In addition, the cellular toxicity of USPIO-CD133 Ab was determined by analyzing cell proliferation, apoptosis, and reactive oxygen species production. Results USPIO-CD133 Ab specifically recognizes in vitro and labels CD133-positive cells, as validated using Prussian blue staining and MRI. The assays of cell proliferation, apoptosis, and reactive oxygen species production showed no significant differences in tumor cells with or without labeling of USPIO-CD133 Ab. In vivo imaging of CD133-positive cells was demonstrated by intravenous injection of USPIO-CD133 Ab in mice with HT29 xenografted tumors. The MRI of HT29 xenografts showed several clusters of hypotensive regions that correlated with CD133 expression and Prussian blue staining for iron. In rat, brain tumors induced by transplacental ENU mutagenesis, several clusters of hypointensive zones were observed in CD133-expressing brain tumors by MRI and intravenously administered USPIO-CD133 Ab. Conclusion Combination of USPIO-CD133 Ab and MRI is valuable in recognizing CD133-expressing tumor cells in vitro, extracellularly labeling for cell tracking and detecting CD133-expressing tumors in xenografted tumors as well as ENU-induced rat brain tumors.

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“…56 Lymphoma cells from >90% of patients with B cell non-Hodgkin's lymphoma (NHL) express this kind of antigen. Importantly, Baio et al 57 used this characteristic of NHL to show the successful use of a commercially available USPIO-anti-CD20 MAb conjugate for MRI imaging in a murine xenotransplant model.…”

Section: Using Spion In Cancer Imaging Applicationsmentioning

confidence: 99%

Superparamagnetic iron oxide nanoparticles for MR imaging of pancreatic cancer: Potential for early diagnosis through targeted strategies

Zhang¹,

Zou²,

Chen³

et al. 2015

Asia-Pac J Clncl Oncology

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Superparamagnetic iron oxide nanoparticles (SPION)-based magnetic resonance imaging is a powerful, noninvasive tool in biomedical imaging. The recent embedding of SPIO in nanoencapsulations that had different controllable surface properties has now made it possible to use SPIO in the imaging of metabolic processes. The two major issues to realize maximized and selective SPIO cancer targeting are the minimization of macrophage uptake and the preferential binding to cancerous cells over healthy neighbor cells. The utility of SPIO has been shown in clinical applications using a series of marketed SPION-based contrast agents. Applications have ranged from detecting inflammatory diseases to the specific identification of cell surface markers expressed on tumors. This review focuses on iron-oxide-based nanoparticles, to include the physiochemical properties of SPION surface engineering and its synthetic methods as well as SPIO imaging applications and specifically targeted SPIO conjugates (e.g. targeted probes) for labeling cancerous, cell-surface molecules. As a specific application of this technology, we discuss its use in the imaging of pancreatic duct adenocarcinoma in addition to its potential for use in early diagnosis through targeted strategies.

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Magnetic resonance imaging at 1.5 T with immunospecific contrast agent in vitro and in vivo in a xenotransplant model

Abstract: MRI at 1.5 T is able to detect USPIO-antibody conjugates targeting a tumor-associated antigen in vitro and in vivo.

Cited by 15 publications

References 13 publications

Polyethylene glycol-covered ultra-small Gd₂O₃nanoparticles for positive contrast at 1.5 T magnetic resonance clinical scanning

Polyethylene glycol-covered ultra-small Gd₂O₃nanoparticles for positive contrast at 1.5 T magnetic resonance clinical scanning

Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging

Superparamagnetic iron oxide nanoparticles for MR imaging of pancreatic cancer: Potential for early diagnosis through targeted strategies

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Magnetic resonance imaging at 1.5 T with immunospecific contrast agent in vitro and in vivo in a xenotransplant model

Abstract: MRI at 1.5 T is able to detect USPIO-antibody conjugates targeting a tumor-associated antigen in vitro and in vivo.

Cited by 15 publications

References 13 publications

Polyethylene glycol-covered ultra-small Gd2O3nanoparticles for positive contrast at 1.5 T magnetic resonance clinical scanning

Polyethylene glycol-covered ultra-small Gd2O3nanoparticles for positive contrast at 1.5 T magnetic resonance clinical scanning

Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using&nbsp;noninvasive molecular magnetic resonance&nbsp;imaging

Superparamagnetic iron oxide nanoparticles for MR imaging of pancreatic cancer: Potential for early diagnosis through targeted strategies

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Polyethylene glycol-covered ultra-small Gd₂O₃nanoparticles for positive contrast at 1.5 T magnetic resonance clinical scanning

Polyethylene glycol-covered ultra-small Gd₂O₃nanoparticles for positive contrast at 1.5 T magnetic resonance clinical scanning

Specific detection of CD133-positive tumor cells with iron oxide nanoparticles labeling using noninvasive molecular magnetic resonance imaging