Feasibility of USPIOs for T<sub>1</sub>-weighted MR molecular imaging of tumor receptors

Liu, Zhetao; Cai, Jiali; Su, Huilan; Yang, Jingxing; Sun, Wenshe; Ma, Yan; Liu, Shiyuan; Zhang, Chunfu

doi:10.1039/c7ra04903j

Cited by 7 publications

(12 citation statements)

References 54 publications

(64 reference statements)

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“…These results indicated that in contrast with traditional iron oxide nanoparticles that are negative T 2 contrast agents, USPIO nanoparticles (<5 nm) can function as simultaneous positive and negative MRI contrast agents. This was in accordance with the findings of other groups [2, 24, 36, 38], which could be attributed to the relatively larger number of Fe 3+ with 5 unpaired electrons over the surface of smaller USPIO nanoparticles with larger surface area [40]. In addition, as the concentration of USPIO nanoparticles increased, there was an enhancement of the longitudinal and transversal relaxation rate, which suggested that they could be used in dynamic enhancement MRI, such as perfusion and permeability.…”

Section: Discussionsupporting

confidence: 94%

“…The core diameter of USPIO nanoparticles was <4.20 nm (3.26 ± 0.87 nm) as shown in TEM image (Figure 1(a)) and core size distribution analysis (Figure 1(b)), indicating significant potential as a positive contrast agent [29, 38–40]. It was found simultaneously from T 1 -weighted and T 2 -weighted images and signals of the phantom in Figures 2(a) and 2(b) a positive enhancement of the T 1 -weighted MR signal and a negative enhancement of the T 2 -weighted MR signal as iron concentration increasing.…”

Section: Resultsmentioning

confidence: 99%

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Imaging Characteristics of USPIO Nanoparticles (<5 nm) as MR Contrast Agent In Vitro and in the Liver of Rats

Wang

et al. 2019

Contrast Media & Molecular Imaging

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Iron nanoparticles have an increasingly more and more important role in MR molecular imaging due to their novel magnetic and surface chemical properties. They provide new possibilities for noninvasive diagnosis and treatment monitoring, especially for tissues that are rich in macrophages. The smaller size and prolongation of the plasma half-life change the in vivo fate of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles captured by liver in reticuloendothelial system (RES) or mononuclear phagocytic system (MPS). However, there is still a lack of MR imaging studies on the liver assessing USPIO nanoparticles <5 nm in size to reflect its absorption and clearance properties. In this study, we used MRI to study the in vitro phantom and in vivo rat liver imaging characteristics of USPIO nanoparticles (<5 nm). The results showed that USPIO nanoparticles (<5 nm) could potentially reduce longitudinal and transverse relaxation times and showed similar T1 relaxation rates compared with commercial gadolinium chelates. In addition, USPIO nanoparticles (<5 nm) in vivo demonstrated both positive (T1) and negative (T2) liver contrast enhancement in healthy rats’ liver. Furthermore, USPIO nanoparticles showed relatively good in vitro biocompatibility and fast clearance (within 45.17 minutes after intravenous injection) in the normal liver. Taken together, these data might inspire a new personalized and precise diagnostic tool and stimulate new applications for specific targeted molecular probes.

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Section: Discussionsupporting

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Imaging Characteristics of USPIO Nanoparticles (<5 nm) as MR Contrast Agent In Vitro and in the Liver of Rats

Wang

et al. 2019

Contrast Media & Molecular Imaging

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“…First, single biomarkers might hinder detection efficiency of existing HCC molecular probes due to tumor heterogeneity. Additionally, iron oxide nanoparticles used in the majority of current HCC imaging studies are utilized as negative (T2) contrast agents, which could result in inaccurate diagnosis[ 25 , 26 ]. However, opportunities to improve these probes also exist.…”

Section: Introductionmentioning

confidence: 99%

“…Nanoparticles exhibit size-dependent magnetic properties. Ultra-small superparamagnetic iron oxide (USPIO) nanoparticles of a small core size (approximately 5 nm) are suggested as optimal positive (T1) contrast agents that enhance T1 and suppress T2 signals induced by reductions in volume of magnetic anisotropy, surface spin disorder, and exposure of iron ions with unpaired electrons[ 26 - 30 ]. Additionally, slow phagocytosis of USPIO nanoparticles by macrophages makes them ideal for liver-tumor MRI[ 31 - 33 ].…”

Section: Introductionmentioning

confidence: 99%

Bi-specific T1 positive-contrast-enhanced magnetic resonance imaging molecular probe for hepatocellular carcinoma in an orthotopic mouse model

Ma¹,

Chen²,

Wang³

et al. 2022

WJGO

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BACKGROUND Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. HCC-targeted magnetic resonance imaging (MRI) is an effective noninvasive diagnostic method that involves targeting clinically-related HCC biomarkers, such as alpha-fetoprotein (AFP) or glypican-3 (GPC3), with iron oxide nanoparticles. However, in vivo studies of HCC-targeted MRI utilize single-target iron oxide nanoprobes as negative (T2) contrast agents, which might weaken their future clinical applications due to tumor heterogeneity and negative MRI contrast. Ultra-small superparamagnetic iron oxide (USPIO) nanoparticles (approximately 5 nm) are potential optimal positive (T1) contrast agents. We previously verified the efficiency of AFP/GPC3-double-antibody-labeled iron oxide MR molecular probe in vitro . AIM To validate the effectiveness of a bi-specific probe in vivo for enhancing T1-weighted positive contrast to diagnose the early-stage HCC. METHODS The single- and double-antibody-conjugated 5-nm USPIO probes, including anti-AFP-USPIO (UA), anti-GPC3-USPIO (UG), and anti-AFP-USPIO-anti-GPC3 (UAG), were synthesized. T1- and T2-weighted MRI were performed on day 10 after establishment of the orthotopic HCC mouse model. Following intravenous injection of U, UA, UG, and UAG probes, T1- and T2-weighted images were obtained at 12, 12, and 32 h post-injection. At the end of scanning, mice were euthanized, and a histologic analysis was performed on tumor samples. RESULTS T1- and T2-weighted MRI showed that absolute tumor-to-background ratios in UAG-treated HCC mice peaked at 24 h post-injection, with the T1- and T2-weighted signals increasing by 46.7% and decreasing by 11.1%, respectively, relative to pre-injection levels. Additionally, T1-weighted contrast in the UAG-treated group at 24 h post-injection was enhanced 1.52-, 2.64-, and 4.38-fold compared to those observed for single-targeted anti-GPC3-USPIO, anti-AFP-USPIO, and non-targeted USPIO probes, respectively. Comparison of U-, UA-, UG-, and UAG-treated tumor sections revealed that UAG-treated mice exhibited increased stained regions compared to those observed in UG- or UA-treated mice. CONCLUSION The bi-specific T1-positive contrast-enhanced MRI probe (UAG) for HCC demonstrated increased specificity and sensitivity to diagnose early-stage HCC irrespective of tumor size and/or heterogeneity.

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“…Generally, contrast agents can be divided into two categories depending on the effect they have on MRI. T 1 contrast agents shorten longitudinal relaxation times, generating bright signals [11][12][13][14][15], whereas T 2 contrast agents shorten transverse relaxation times, generating dark signals [16,17]. Even though T 1 contrast agents, such as Gd-DTPA (gadolinium diethylenetriaminepentacetate), are highly advantageous for diagnostic imaging, since they generate bright images, the renal toxicity of Gd-based contrast agents should not be ignored [18,19].…”

Section: Introductionmentioning

confidence: 99%

Uniform Fe₃O₄/Gd₂O₃-DHCA nanocubes for dual-mode magnetic resonance imaging

Miao

Peng

et al. 2020

Beilstein J. Nanotechnol.

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The multimodal magnetic resonance imaging (MRI) technique has been extensively studied over the past few years since it offers complementary information that can increase diagnostic accuracy. Simple methods to synthesize contrast agents are necessary for the development of multimodal MRI. Herein, uniformly distributed Fe3O4/Gd2O3 nanocubes for T 1–T 2 dual-mode MRI contrast agents were successfully designed and synthesized. In order to increase hydrophilicity and biocompatibility, the nanocubes were coated with nontoxic 3,4-dihydroxyhydrocinnamic acid (DHCA). The results show that iron (Fe) and gadolinium (Gd) were homogeneously distributed throughout the Fe3O4/Gd2O3-DHCA (FGDA) nanocubes. Relaxation time analysis was performed on the images obtained from the 3.0 T scanner. The results demonstrated that r 1 and r 2 maximum values were 67.57 ± 6.2 and 24.2 ± 1.46 mM−1·s−1, respectively. In vivo T 1- and T 2-weighted images showed that FGDA nanocubes act as a dual-mode contrast agent enhancing MRI quality. Overall, these experimental results suggest that the FGDA nanocubes are interesting tools that can be used to increase MRI quality, enabling accurate clinical diagnostics.

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Feasibility of USPIOs for T₁-weighted MR molecular imaging of tumor receptors

Abstract: USPIOs having a superior T1 contrast effect could only be used for T2-weighted, but not for T1-weighted MR tumor receptor imaging.

Cited by 7 publications

References 54 publications

Imaging Characteristics of USPIO Nanoparticles (<5 nm) as MR Contrast Agent In Vitro and in the Liver of Rats

Imaging Characteristics of USPIO Nanoparticles (<5 nm) as MR Contrast Agent In Vitro and in the Liver of Rats

Bi-specific T1 positive-contrast-enhanced magnetic resonance imaging molecular probe for hepatocellular carcinoma in an orthotopic mouse model

Uniform Fe₃O₄/Gd₂O₃-DHCA nanocubes for dual-mode magnetic resonance imaging

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Feasibility of USPIOs for T1-weighted MR molecular imaging of tumor receptors

Abstract: USPIOs having a superior T1 contrast effect could only be used for T2-weighted, but not for T1-weighted MR tumor receptor imaging.

Cited by 7 publications

References 54 publications

Imaging Characteristics of USPIO Nanoparticles (<5 nm) as MR Contrast Agent In Vitro and in the Liver of Rats

Imaging Characteristics of USPIO Nanoparticles (<5 nm) as MR Contrast Agent In Vitro and in the Liver of Rats

Bi-specific T1 positive-contrast-enhanced magnetic resonance imaging molecular probe for hepatocellular carcinoma in an orthotopic mouse model

Uniform Fe3O4/Gd2O3-DHCA nanocubes for dual-mode magnetic resonance imaging

Contact Info

Product

Resources

About

Feasibility of USPIOs for T₁-weighted MR molecular imaging of tumor receptors

Uniform Fe₃O₄/Gd₂O₃-DHCA nanocubes for dual-mode magnetic resonance imaging