In vivo Imaging Biodistribution Profile of a New Macrocyclic Gadolinium Chelate as a Highly Stable Multifunctional MRI Contrast Agent

A new macromolecular biocompatible gadolinium chelate complex (PAI-N2-DOTA-Gd) as a liver-specific magnetic resonance imaging (MRI) contrast agent was synthesised and evaluated. An aspartic acid–isoleucine copolymer was chemically linked with Gd-DOTA via ethylenediamine to give PAI-N2-DOTA-Gd. In vitro, the T1-relaxivity of PAI-N2-DOTA-Gd (14.38 mmol–1⋅L⋅s–1, 0.5 T) was much higher than that of the clinically used Gd-DOTA (4.96 mmol–1⋅L⋅s–1, 0.5 T), with obvious imaging signal enhancement. In the imaging experiments in vivo, PAI-N2-DOTA-Gd exhibited good liver selectivity, and had a greater intensity enhancement (68.8 ± 5.6 %) and a longer imaging window time (30–70 min), compared to Gd-DOTA (21.1 ± 5.3 %, 10–30 min). Furthermore, the in vivo histological studies of PAI-N2-DOTA-Gd showed a low acute toxicity and desirable biocompatibility. The results of this study indicate that PAI-N2-DOTA-Gd is a feasible liver-specific contrast agent for MRI.

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In Vivo Imaging with a Cell-Permeable Porphyrin-Based MRI Contrast Agent

Chemistry & Biology ◽

10.1016/j.chembiol.2010.05.009 ◽

2010 ◽

Vol 17 (6) ◽

pp. 665-673 ◽

Cited By ~ 53

Author(s):

Taekwan Lee ◽

Xiao-an Zhang ◽

Shanta Dhar ◽

Henryk Faas ◽

Stephen J. Lippard ◽

...

Keyword(s):

Contrast Agent ◽

In Vivo Imaging ◽

Mri Contrast Agent ◽

Mri Contrast ◽

A Cell

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Biocompatibility of Bacterial Magnetosomes as MRI Contrast Agent: A Long-Term In Vivo Follow-Up Study

Nanomaterials ◽

10.3390/nano11051235 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1235

Author(s):

Xiaohui Nan ◽

Wenjia Lai ◽

Dan Li ◽

Jiesheng Tian ◽

Zhiyuan Hu ◽

...

Keyword(s):

Contrast Agent ◽

Magnetic Domain ◽

Bilayer Membrane ◽

The Body ◽

Mri Contrast Agent ◽

Mri Imaging ◽

Mri Contrast

Derived from magnetotactic bacteria (MTB), magnetosomes consist of magnetite crystals enclosed within a lipid bilayer membrane and are known to possess advantages over artificially synthesized nanoparticles because of the narrow size distribution, uniform morphology, high purity and crystallinity, single magnetic domain, good biocompatibility, and easy surface modification. These unique properties have increasingly attracted researchers to apply bacterial magnetosomes (BMs) in the fields of biology and medicine as MRI imaging contrast agents. Due to the concern of biosafety, a long-term follow-up of the distribution and clearance of BMs after entering the body is necessary. In this study, we tracked changes of BMs in major organs of mice up to 135 days after intravenous injection using a combination of several techniques. We not only confirmed the liver as the well-known targeted organs of BMs, but also found that BMs accumulated in the spleen. Besides, two major elimination paths, as well as the approximate length of time for BMs to be cleared from the mice, were revealed. Together, the results not only confirm that BMs have high biocompatibility, but also provide a long-term in-vivo assessment which may further help to forward the clinical applications of BMs as an MRI contrast agent.

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RGD-Peptide Functionalization Affects the In Vivo Diffusion of a Responsive Trimeric MRI Contrast Agent through Interactions with Integrins

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.1c00264 ◽

2021 ◽

Author(s):

Giuseppe Gambino ◽

Tanja Gambino ◽

Liam Connah ◽

Francesca La Cava ◽

Henry Evrard ◽

...

Keyword(s):

Contrast Agent ◽

Rgd Peptide ◽

Mri Contrast Agent ◽

Mri Contrast ◽

Peptide Functionalization

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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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Abstract 403: Tracking the Migration of Porcine Mesenchymal Stem Cells with the MRI Contrast Agent Ferex in an AAA Model

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.32.suppl_1.a403 ◽

2012 ◽

Vol 32 (suppl_1) ◽

Author(s):

Rami Tadros ◽

Bhakti Rawal ◽

Karen Briley-Saebo ◽

David O’Connor ◽

Dan Han ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Contrast Agent ◽

Lentiviral Vector ◽

Relaxation Times ◽

Mri Contrast Agent ◽

Signal Loss ◽

Post Transplantation ◽

Mri Contrast

Introduction: Mesenchymal stem cells (MSC) are being investigated in porcine abdominal aortic aneurysm (PAAA) models for their repair potential. This study uses MSCs labeled with the MRI contrast agent Ferex to non-invasively evaluate MSC migration in-vivo. Methods: MSCs from 6 pigs were isolated from bone marrow via Ficoll Paque separation and expanded in culture. Using a Lentiviral vector, MSC from all 6 pigs were transfected with green florescent protein (GFP). MSCs from 4 of these pigs were also labeled with 200μg/ml Ferex using Poly-L-Lysine and then analyzed for Ferex uptake and viability. Preservation of the MSC phenotype was confirmed using flow cytometry by detecting positive CD90 and negative CD45 and CD117. Transmission electron microscopy established that Ferex localized to lysosomes. MSCs were then injected into the adventitia of the PAAA. In-vivo MRI was performed using multiple echo gradient echo sequences. Effective transverse relaxation times (T2* values) were calculated on a pixel-by-pixel basis as a function of time post cell transplantation. Results: Ferex labeled MSCs were visible post transplantation at 4, 11, 15 and 21 days using MRI. The MRI signal void (decreased T2* values) correlated with the presence of Ferex within the PAAA. This signal loss progressively expanded circumferentially at each study interval representing cellular movement. MSC migration and localization were confirmed with GFP visualization on fluorescence microscopy and immunohistochemistry. In-vivo MRI signals also correlate with iron deposition on Perl’s stain. Conclusion: Ferex can be used as an in-vivo tracking agent of MSCs in PAAA models.

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