Imaging Tissue Physiology In Vivo by Use of Metal Ion-Responsive MRI Contrast Agents

Paramagnetic metal ion complexes, mostly based on gadolinium (Gd3+), have been used for over 30 years as magnetic resonance imaging (MRI) contrast agents. Gd3+-based contrast agents have a strong influence on T1 relaxation times and are consequently the most commonly used agents in both the clinical and research environments. Zinc is an essential element involved with over 3000 different cellular proteins, and disturbances in tissue levels of zinc have been linked to a wide range of pathologies, including Alzheimer’s disease, prostate cancer, and diabetes mellitus. MR contrast agents that respond to the presence of Zn2+ in vivo offer the possibility of imaging changes in Zn2+ levels in real-time with the superior spatial resolution offered by MRI. Such responsive agents, often referred to as smart agents, are typically composed of a paramagnetic metal ion with a ligand encapsulating it and one or more chelating units that selectively bind with the analyte of interest. Translation of these agents into clinical radiology is the next goal. In this review, we discuss Gd3+-based MR contrast agents that respond to a change in local Zn2+ concentration.

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THE PARAMAGNETIC PILLARED BENTONITES AS DIGESTIVE TRACT MRI CONTRAST AGENTS

International Journal of Modern Physics B ◽

10.1142/s0217979210064411 ◽

2010 ◽

Vol 24 (06n07) ◽

pp. 780-787 ◽

Cited By ~ 1

Author(s):

MILOŠ MOJOVIĆ ◽

MARKO DAKOVIĆ ◽

MIA OMERAŠEVIĆ ◽

ZORICA MOJOVIĆ ◽

PREDRAG BANKOVIĆ ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Side Effects ◽

Contrast Agents ◽

Digestive Tract ◽

Imaging Techniques ◽

Relaxation Times ◽

Mri Contrast Agents ◽

Paramagnetic Species ◽

Mri Contrast ◽

Wide Range

The increased use of imaging techniques in diagnostic studies, such as MRI, has contributed to the development of the wide range of new materials which could be successfully used as image improving agents. However, there is a lack of such substances in the area of gastrointestinal tract MRI. Many of the traditionally popular relaxation altering agents show poor results and disadvantages provoking black bowel, side effects of diarrhea and the presence of artifacts arising from clumping. Paramagnetic species seem to be potentially suitable agents for these studies, but contrast opacification has been reported and less than 60% of the gastrointestinal tract magnetic resonance scans showed improved delineation of abdominal pathologies. The new solution has been proposed as zeolites or smectite clays (hectorite and montmorillonite) enclosing of paramagnetic metal ions obtained by ion-exchange methods. However, such materials have problems of leakage of paramagnetic ions causing the appearance of the various side-effects. In this study we show that Co +2 and Dy +3 paramagnetic-pillared bentonites could be successfully used as MRI digestive tract non-leaching contrast agents, altering the longitudinal and transverse relaxation times of fluids in contact with the clay minerals.

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Study on Establishing Reference Safe Concentrations of MRI Contrast Agents for Optimized Images: Paramagnetic Gd-DTPA-BMEA and Superparamagnetic Ferucarbotran

Applied Sciences ◽

10.3390/app11031165 ◽

2021 ◽

Vol 11 (3) ◽

pp. 1165

Author(s):

Wen-Tien Hsiao ◽

Yi-Hong Chou ◽

Jhong-Wei Tu ◽

Ai-Yih Wang ◽

Lu-Han Lai

Keyword(s):

Contrast Agent ◽

Contrast Agents ◽

Mri Contrast Agents ◽

Mri Contrast Agent ◽

In Vitro Experiments ◽

Mri Contrast ◽

In Vivo Experiments ◽

Contrast Agent Injection

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%; all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 μL, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

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Comparison of divalent transition metal ion paraCEST MRI contrast agents

JBIC Journal of Biological Inorganic Chemistry ◽

10.1007/s00775-013-1059-4 ◽

2013 ◽

Vol 19 (2) ◽

pp. 191-205 ◽

Cited By ~ 50

Author(s):

Sarina J. Dorazio ◽

Abiola O. Olatunde ◽

Pavel B. Tsitovich ◽

Janet R. Morrow

Keyword(s):

Transition Metal ◽

Contrast Agents ◽

Metal Ion ◽

Mri Contrast Agents ◽

Transition Metal Ion ◽

Mri Contrast

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Dynamic, Simultaneous Concentration Mapping of Multiple MRI Contrast Agents with Dual Contrast - Magnetic Resonance Fingerprinting

Scientific Reports ◽

10.1038/s41598-019-56531-7 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Christian E. Anderson ◽

Mette Johansen ◽

Bernadette O. Erokwu ◽

He Hu ◽

Yuning Gu ◽

...

Keyword(s):

Magnetic Resonance ◽

Contrast Agents ◽

Ex Vivo ◽

Single Agent ◽

Mri Contrast Agents ◽

Mri Contrast Agent ◽

Spatiotemporal Resolution ◽

Mri Contrast ◽

Contrast Magnetic Resonance

AbstractSynchronous assessment of multiple MRI contrast agents in a single scanning session would provide a new “multi-color” imaging capability similar to fluorescence imaging but with high spatiotemporal resolution and unlimited imaging depth. This multi-agent MRI technology would enable a whole new class of basic science and clinical MRI experiments that simultaneously explore multiple physiologic/molecular events in vivo. Unfortunately, conventional MRI acquisition techniques are only capable of detecting and quantifying one paramagnetic MRI contrast agent at a time. Herein, the Dual Contrast – Magnetic Resonance Fingerprinting (DC-MRF) methodology was extended for in vivo application and evaluated by simultaneously and dynamically mapping the intra-tumoral concentration of two MRI contrast agents (Gd-BOPTA and Dy-DOTA-azide) in a mouse glioma model. Co-registered gadolinium and dysprosium concentration maps were generated with sub-millimeter spatial resolution and acquired dynamically with just over 2-minute temporal resolution. Mean tumor Gd and Dy concentration measurements from both single agent and dual agent DC-MRF studies demonstrated significant correlations with ex vivo mass spectrometry elemental analyses. This initial in vivo study demonstrates the potential for DC-MRF to provide a useful dual-agent MRI platform.

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LDL-mimetic lipid nanoparticles prepared by surface KAT ligation for in vivo MRI of atherosclerosis

Chemical Science ◽

10.1039/d0sc04106h ◽

2020 ◽

Vol 11 (44) ◽

pp. 11998-12008

Author(s):

Alessandro Fracassi ◽

Jianbo Cao ◽

Naoko Yoshizawa-Sugata ◽

Éva Tóth ◽

Corey Archer ◽

...

Keyword(s):

Contrast Agents ◽

Fluorescent Dyes ◽

Lipid Nanoparticles ◽

Mri Contrast Agents ◽

Mri Contrast ◽

Mimetic Peptide

LDL-mimetic lipid nanoparticles, decorated with MRI contrast agents and fluorescent dyes, were prepared by the covalent attachments of an apoB100-mimetic peptide, Gd(iii)-chelate, and rhodamine to enhance atherosclerosis in the in vivo imaging.

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

Beilstein Journal of Nanotechnology ◽

10.3762/bjnano.11.84 ◽

2020 ◽

Vol 11 ◽

pp. 1000-1009

Author(s):

Miao Qin ◽

Yueyou Peng ◽

Mengjie Xu ◽

Hui Yan ◽

Yizhu Cheng ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Contrast Agents ◽

Mri Contrast Agents ◽

Clinical Diagnostics ◽

Resonance Imaging ◽

Dual Mode ◽

Mri Contrast ◽

Magnetic Resonance Imaging Mri

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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The In Vivo Radiosensitizing Effect of Gold Nanoparticles Based MRI Contrast Agents

Small ◽

10.1002/smll.201302303 ◽

2014 ◽

Vol 10 (6) ◽

pp. 1116-1124 ◽

Cited By ~ 79

Author(s):

Imen Miladi ◽

Christophe Alric ◽

Sandrine Dufort ◽

Pierre Mowat ◽

Aurélie Dutour ◽

...

Keyword(s):

Gold Nanoparticles ◽

Contrast Agents ◽

Mri Contrast Agents ◽

Mri Contrast ◽

Radiosensitizing Effect

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Ultrasmall Europium, Gadolinium, and Dysprosium Oxide Nanoparticles: Polyol Synthesis, Properties, and Biomedical Imaging Applications

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557520666200604163452 ◽

2020 ◽

Vol 20 (17) ◽

pp. 1767-1780 ◽

Cited By ~ 1

Author(s):

Huan Yue ◽

Ja Young Park ◽

Yongmin Chang ◽

Gang Ho Lee

Keyword(s):

Contrast Agents ◽

In Vivo Imaging ◽

Biomedical Imaging ◽

Mri Contrast Agents ◽

Polyol Synthesis ◽

Imaging Agents ◽

Bibliographic Databases ◽

Mri Contrast ◽

X Ray

Imaging agents are crucial in diagnosing diseases. Ultrasmall lanthanide oxide (Ln2O3) nanoparticles (NPs) (Ln = Eu, Gd, and Dy) are promising materials as high-performance imaging agents because of their excellent magnetic, optical, and X-ray attenuation properties which can be applied as magnetic resonance imaging (MRI), fluorescence imaging (FI), and X-ray computed tomography (CT) agents, respectively. Ultrasmall Ln2O3 NPs (Ln = Eu, Gd, and Dy) are reviewed here. The reviewed topics include polyol synthesis, characterization, properties, and biomedical imaging applications of ultrasmall Ln2O3 NPs. Recently published papers were used as bibliographic databases. A polyol method is a simple and efficient one-pot synthesis for preparing ultrasmall Ln2O3 NPs. Ligand-coated ultrasmall Ln2O3 NPs have good colloidal stability, biocompatibility, and renal excretion ability suitable for in vivo imaging applications. Ultrasmall Eu2O3 NPs display photoluminescence in the red region suitable for use as FI agents. Ultrasmall Gd2O3 NPs have r1 values higher than those of commercial molecular contrast agents and r2/r1 ratios close to 1, which make them eligible for use as T1 MRI contrast agents. Ultrasmall Dy2O3 NPs exhibit high r2 and negligible r1 values, which make them suitable for use as T2 MRI contrast agents. All ultrasmall Ln2O3 NPs have high X-ray attenuation powers which make them suitable for use as CT contrast agents. Unmixed, mixed, or doped ultrasmall Ln2O3 NPs with different Ln are extremely useful for in vivo imaging applications in MRI, CT, FI, MRI-CT, MRI-FI, CT-FI, and MRI-CT-FI.

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