scholarly journals Amphiphilic branched polymer-nitroxides conjugate as a nanoscale agent for potential magnetic resonance imaging of multiple objects in vivo

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaoming Wang ◽  
Shiwei Guo ◽  
Zhiqian Li ◽  
Qiang Luo ◽  
Yan Dai ◽  
...  

Abstract Background In order to address the potential toxicity of metal-based magnetic resonance imaging (MRI) contrast agents (CAs), a concept of non-metallic MRI CAs has emerged. Currently, paramagnetic nitroxides (such as (2,2,5,5-tetramethylpyrrolidine-1-oxyl, PROXYL), (2,2,6,6-tetramethylpiperidine-1-oxide, TEMPO), etc.) are being extensively studied because their good stability and imaging mechanism are similar to metal-based contrast agents (such as Gd3+ chelate-based clinical CAs). However, a lower relaxivity and rapid in vivo metabolism of nitroxides remain to be addressed. Previous studies have demonstrated that the construction of macromolecular nitroxides contrast agents (mORCAs) is a promising solution through macromolecularization of nitroxides (i.e., use of large molecules to carry nitroxides). Macromolecular effects not only increase the stability of nitroxides by limiting their exposure to reductive substances in the body, but also improve the overall 1H water relaxation by increasing the concentration of nitroxides and slowing the molecular rotation speed. Results Branched pDHPMA-mPEG-Ppa-PROXYL with a high molecular weight (MW = 160 kDa) and a nitroxides content (0.059 mmol/g) can form a nanoscale (~ 28 nm) self-assembled aggregate in a water environment and hydrophobic PROXYL can be protected by a hydrophilic outer layer to obtain strong reduction resistance in vivo. Compared with a small molecular CA (3-Carboxy-PROXYL (3-CP)), Branched pDHPMA-mPEG-Ppa-PROXYL displays three prominent features: (1) its longitudinal relaxivity (0.50 mM− 1 s− 1) is about three times that of 3-CP (0.17 mM− 1 s− 1); (2) the blood retention time of nitroxides is significantly increased from a few minutes of 3-CP to 6 h; (3) it provides long-term and significant enhancement in MR imaging of the tumor, liver, kidney and cardiovascular system (heart and aortaventralis), and this is the first report on nitroxides-based MRI CAs for imaging the cardiovascular system. Conclusions As a safe and efficient candidate metal-free magnetic resonance contrast agent, Branched pDHPMA-mPEG-Ppa-PROXYL is expected to be used not only in imaging the tumor, liver and kidney, but also the cardiovascular system, which expands the application scope of these CAs. Graphical abstract

2021 ◽  
Author(s):  
Xiaoming Wang ◽  
Shiwei Guo ◽  
Zhiqian Li ◽  
Qiang Luo ◽  
Yan Dai ◽  
...  

Abstract Background: In order to solve the potential toxicity of metal-based Magnetic resonance imaging (MRI) contrast agents (CAs), a concept of non-metallic MRI CAs has emerged. Currently, paramagnetic nitroxides (such as (2, 2, 5, 5-tetramethylpyrrolidine-1-oxyl, PROXYL), (2, 2, 6, 6-tetramethylpiperidine-1-oxide, TEMPO), etc.) are being extensively studied because their good stability and imaging mechanism are similar to metal based contrast agents (such as Gd3+ chelate-based clinical CAs). However, nitroxides lower relaxivity and metabolizes rapidly in vivo are still challenge. Previous researches have proven that the construction of macromolecular nitroxides contrast agents (mORCAs) is a promising solution through the macromolecularization of nitroxides (ie, large molecules carry nitroxides). Macromolecular effects not only improve the stability of nitroxides by limiting their exposure to reductive substances in the body, but also improve the overall 1H water relaxation by increasing the concentration of nitroxides and slowing the molecular rotation speed. Results: Branched pDHPMA-mPEG-Ppa-PROXYL with high molecular weight (MW=160 kDa) and nitroxides content (0.059 mmol/g), it can form a nanoscale (~ 28 nm) self-assembled aggregate in a water environment and hydrophobic PROXYL can be protected by the hydrophilic outer layer to obtain the strong reduction resistance in vivo. Compared with the small molecular 3-Carboxy-PROXYL (3-CP), Branched pDHPMA-mPEG-Ppa-PROXYL displays there prominent performance: 1) its longitudinal relaxivity (0.50 mM-1 s-1) is about three times that of the 3-CP (0.17 mM-1 s-1); 2) the blood retention time of nitroxides is increased significantly from a few minutes of 3-CP to 6 h; 3) it could provide long-term and significant enhancement in MR imaging of the tumor, liver, kidney and cardiovascular system (heart and aortaventralis), and this is the first report on nitroxides-based MRI CAs for imaging the cardiovascular system. Conclusions: As a safe and efficient candidate metal-free magnetic resonance contrast agent, Branched pDHPMA-mPEG-Ppa-PROXYL is expected to be used not only in tumor, liver and kidney imaging, but also in cardiovascular system imaging, which expands the application scope of this kind of CAs.


2020 ◽  
Vol 11 ◽  
pp. 1000-1009
Author(s):  
Miao Qin ◽  
Yueyou Peng ◽  
Mengjie Xu ◽  
Hui Yan ◽  
Yizhu Cheng ◽  
...  

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.


2015 ◽  
Vol 8s1 ◽  
pp. MRI.S23559 ◽  
Author(s):  
Matthew S. Fox ◽  
Jeffrey M. Gaudet ◽  
Paula J. Foster

Fluorine-19 (19F)-based contrast agents for magnetic resonance imaging stand to revolutionize imaging-based research and clinical trials in several fields of medical intervention. First, their use in characterizing in vivo cell behavior may help bring cellular therapy closer to clinical acceptance. Second, their use in lung imaging provides novel noninvasive interrogation of the ventilated airspaces without the need for complicated, hard-to-distribute hardware. This article reviews the current state of 19F-based cell tracking and lung imaging using magnetic resonance imaging and describes the link between the methods across these fields and how they may mutually benefit from solutions to mutual problems encountered when imaging 19F-containing compounds, as well as hardware and software advancements.


Nanoscale ◽  
2015 ◽  
Vol 7 (28) ◽  
pp. 11899-11903 ◽  
Author(s):  
M. Perrier ◽  
A. Gallud ◽  
A. Ayadi ◽  
S. Kennouche ◽  
C. Porredon ◽  
...  

Ultra small Gd3+/[Fe(CN)6]3− nanoparticles are investigated in vivo as contrast agents for Magnetic Resonance Imaging.


2016 ◽  
Vol 4 (45) ◽  
pp. 7241-7248 ◽  
Author(s):  
Qin Zhu ◽  
Heng Yang ◽  
Yuanyuan Li ◽  
Yu Tian ◽  
Wei Wang ◽  
...  

HP-DO3A-based amphiphilic magnetic resonance imaging (MRI) contrast agents show electrostatic self-assembly ability with polyelectrolytes, good biocompatibility, and significant contrast enhancement in in vivo imaging.


2019 ◽  
Author(s):  
Hamilton Lee ◽  
Jenica Lumata ◽  
Michael A. Luzuriaga ◽  
Candace Benjamin ◽  
Olivia Brohlin ◽  
...  

<div><div><div><p>Many contrast agents for magnetic resonance imaging are based on gadolinium, however side effects limit their use in some patients. Organic radical contrast agents (ORCAs) are potential alternatives, but are reduced rapidly in physiological conditions and have low relaxivities as single molecule contrast agents. Herein, we use a supramolecular strategy where cucurbit[8]uril binds with nanomolar affinities to ORCAs and protects them against biological reductants to create a stable radical in vivo. We further over came the weak contrast by conjugating this complex on the surface of a self-assembled biomacromolecule derived from the tobacco mosaic virus.</p></div></div></div>


Author(s):  
Anton Popov ◽  
Maxim Artemovich Abakumov ◽  
Irina Savintseva ◽  
Artem Ermakov ◽  
Nelly Popova ◽  
...  

Gd-based complexes are widely used as magnetic resonance imaging (MRI) contrast agents. The safety of previously approved contrast agents is questionable and is being re-assessed. The main causes of concern...


Nanomaterials ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 879 ◽  
Author(s):  
Maria Şologan ◽  
Francesco Padelli ◽  
Isabella Giachetti ◽  
Domenico Aquino ◽  
Mariangela Boccalon ◽  
...  

Gold nanoparticles carrying fluorinated ligands in their monolayer are, by themselves, contrast agents for 19F magnetic resonance imaging displaying high sensitivity because of the high density of fluorine nuclei achievable by grafting suitable ligands on the gold core surface. Functionalization of these nanoparticles with Gd(III) chelates allows adding a further functional activity to these systems, developing materials also acting as contrast agents for proton magnetic resonance imaging. These dual mode contrast agents may allow capitalizing on the benefits of 1H and 19F magnetic resonance imaging in a single diagnostic session. In this work, we describe a proof of principle of this approach by studying these nanoparticles in a high field preclinical scanner. The Gd(III) centers within the nanoparticles monolayer shorten considerably the 19F T1 of the ligands but, nevertheless, these systems display strong and sharp NMR signals which allow recording good quality 19F MRI phantom images at nanoparticle concentration of 20 mg/mL after proper adjustment of the imaging sequence. The Gd(III) centers also influence the T1 relaxation time of the water protons and high quality 1H MRI images could be obtained. Gold nanoparticles protected by hydrogenated ligands and decorated with Gd(III) chelates are reported for comparison as 1H MRI contrast agents.


Processes ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 462 ◽  
Author(s):  
Karina Nava Andrade ◽  
Gregorio Guadalupe Carbajal Arízaga ◽  
José Antonio Rivera Mayorga

In this work, we explore the synthesis of layered double hydroxide (LDH) particles containing different molar ratios of Gd3+ and Dy3+ cations. A single crystalline phase was obtained for Zn2.0Al0.75Gd0.125Dy0.125-LDH and Zn2.0Al0.5Gd0.25Dy0.25-LDH, and their efficiency as contrast agents was evaluated by T1- and T2-weighted magnetic resonance imaging (MRI). Both GdDy-LDHs exhibited longitudinal relaxivity (r1) higher than a commercial reference. The highest contrast in the T1 mode was achieved with the Zn2.0Al0.75Gd0.125Dy0.125-LDH, which contained the lowest concentration of lanthanides; this efficiency is related to the lowest amount of carbonate anions complexing the lanthanide sites. On the contrary, the best contrast in the T2 mode was achieved with Zn2.0Al0.5Gd0.25Dy0.25-LDH. Zn2.0Al0.75Gd0.125Dy0.125-LDH and Zn2.0Al0.5Gd0.25Dy0.25-LDH presented r2/r1 ratios of 7.9 and 22.5, respectively, indicating that the inclusion of gadolinium and dysprosium into layered structures is a promising approach to the development of efficient bimodal (T1/T2) MRI contrast agents.


Sign in / Sign up

Export Citation Format

Share Document