scholarly journals Nanosized T1 MRI Contrast Agent Based on a Polyamidoamine as Multidentate Gd Ligand

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 174
Author(s):  
Paolo Arosio ◽  
Davide Cicolari ◽  
Amedea Manfredi ◽  
Francesco Orsini ◽  
Alessandro Lascialfari ◽  
...  

A linear polyamidoamine (PAA) named BAC-EDDS, containing metal chelating repeat units composed of two tert-amines and four carboxylic groups, has been prepared by the aza-Michael polyaddition of ethylendiaminodisuccinic (EDDS) with 2,2-bis(acrylamido)acetic acid (BAC). It was characterized by size exclusion chromatography (SEC), FTIR, UV–Vis and NMR spectroscopies. The pKa values of the ionizable groups of the repeat unit were estimated by potentiometric titration, using a purposely synthesized molecular ligand (Agly-EDDS) mimicking the structure of the BAC-EDDS repeat unit. Dynamic light scattering (DLS) and ζ-potential analyses revealed the propensity of BAC-EDDS to form stable nanoaggregates with a diameter of approximately 150 nm at pH 5 and a net negative charge at physiological pH, in line with an isoelectric point <2. BAC-EDDS stably chelated Gd (III) ions with a molar ratio of 0.5:1 Gd (III)/repeat unit. The stability constant of the molecular model Gd-Agly-EDDS (log K = 17.43) was determined as well, by simulating the potentiometric titration through the use of Hyperquad software. In order to comprehend the efficiency of Gd-BAC-EDDS in contrasting magnetic resonance images, the nuclear longitudinal (r1) and transverse (r2) relaxivities as a function of the externally applied static magnetic field were investigated and compared to the ones of commercial contrast agents. Furthermore, a model derived from the Solomon–Bloembergen–Morgan theory for the field dependence of the NMR relaxivity curves was applied and allowed us to evaluate the rotational correlation time of the complex (τ = 0.66 ns). This relatively high value is due to the dimensions of Gd-BAC-EDDS, and the associated rotational motion causes a peak in the longitudinal relaxivity at ca. 75 MHz, which is close to the frequencies used in clinics. The good performances of Gd-BAC-EDDS as a contrast agent were also confirmed through in vitro magnetic resonance imaging experiments with a 0.2 T magnetic field.

2021 ◽  
Vol 20 ◽  
pp. 153303382110365
Author(s):  
Lin Qiu ◽  
Shuwen Zhou ◽  
Ying Li ◽  
Wen Rui ◽  
Pengfei Cui ◽  
...  

Bifunctional magnetic/fluorescent core-shell silica nanospheres (MNPs) encapsulated with the magnetic Fe3O4 core and a derivate of 8-amimoquinoline (N-(quinolin-8-yl)-2-(3-(triethoxysilyl) propylamino) acetamide) (QTEPA) into the shell were synthesized. These functional MNPs were prepared with a modified stöber method and the formed Fe3O4@SiO2-QTEPA core-shell nanocomposites are biocompatible, water-dispersible, and stable. These prepared nanoparticles were characterized by X-ray power diffraction (XRD), transmission electron microscopy (TEM), thermoelectric plasma Quad II inductively coupled plasma mass spectrometry (ICP-MS), superconducting quantum interference device (SQUID), TG/DTA thermal analyzer (TGA) and Fourier transform infrared spectroscopy (FTIR). Further application of the nanoparticles in detecting Zn2+ was confirmed by the fluorescence experiment: the nanosensor shows high selectivity and sensitivity to Zn2+ with a 22-fold fluorescence emission enhancement in the presence of 10 μM Zn2+. Moreover, the transverse relaxivity measurements show that the core-shell MNPs have T2 relaxivity (r2) of 155.05 mM−1 S−1 based on Fe concentration on the 3.0 T scanner, suggesting that the compound can be used as a negative contrast agent for MRI. Further in vivo experiments showed that these MNPs could be used as MRI contrast agent. Therefore, the new nanosensor provides the dual modality of magnetic resonance imaging and optical imaging.


F1000Research ◽  
2014 ◽  
Vol 2 ◽  
pp. 252
Author(s):  
Rachael A Panizzo ◽  
David G Gadian ◽  
Jane C Sowden ◽  
Jack A Wells ◽  
Mark F Lythgoe ◽  
...  

Efficacy of neural stem/progenitor cell (NPC) therapies after cerebral ischaemia could be better evaluated by monitoring in vivo migration and distribution of cells post-engraftment in parallel with analysis of lesion volume and functional recovery. Magnetic resonance imaging (MRI) is ideally placed to achieve this, but still poses several challenges. We show that combining the ferumoxide MRI contrast agent Endorem with protamine sulphate (FePro) improves iron oxide uptake in cells compared to Endorem alone and is non-toxic. Hence FePro complex is a better contrast agent than Endorem for monitoring NPCs. FePro complex-labelled NPCs proliferated and differentiated normally in vitro, and upon grafting into the brain 48 hours post-ischaemia they were detected in vivo by MRI. Imaging over four weeks showed the development of a confounding endogenous hypointense contrast evolution at later timepoints within the lesioned tissue. This was at least partly due to accumulation within the lesion of macrophages and endogenous iron. Neither significant NPC migration, assessed by MRI and histologically, nor a reduction in the ischaemic lesion volume was observed in NPC-grafted brains.  Crucially, while MRI provides reliable information on engrafted cell location early after an ischaemic insult, pathophysiological changes to ischaemic lesions can interfere with cellular imaging at later timepoints.


2021 ◽  
Vol 13 (9) ◽  
pp. 1611-1621
Author(s):  
Rong Guo ◽  
Binbin Ma ◽  
Jiaqiu Nie

This study aimed to explore the value of preoperative mammography in the differential diagnosis of benign and malignant tumors of nipple discharge. A biocompatible T1 contrast agent KMnF3 nanoparticle was first developed in the research, and then RGD-coupled KMnF3 nanoparticles were further synthesized as a highly sensitive tumor-targeted magnetic resonance imaging (MRI) contrast agent. While the nanoparticle was characterized physically, cytotoxicity test and MRI test in breast cancer mice were performed, and the excised tumors were subjected to immunostaining and tumor electron microscope section processing. At the same time, 60 patients with nipple discharge were screened to participate in the research, and the prepared MRI nano contrast agent was used for the differential diagnosis of breast benign/malignant tumors of nipple discharge. In the experiment, the synthetic nanoparticles were tested by Fourier transformed infrared (FTIR), which proved that the designed RGDtu/KMnF3 nanoparticles were successfully synthesized. The quantitative analysis of the synthesized nanoparticles showed that the relaxation efficiency reached 23.12 mM−1s−1, and there was no obvious toxicity. After staining, the microscope showed that the tumor was proliferating. After intravenous injection of low-dose RGDtu/KMnF3 contrast agent, nanoparticles were found in the tumor tissue. It was found that the synthesized nanoparticles enhanced the contrast of tumors with a volume of less than 50 mm3 by observing tumor slices. The imaging of the patient’s breast showed that the X-ray classification of galactography based on this contrast agent was statistically significant in distinguishing benign/malignant lesions of nipple discharge (X2 = 58.700, P < 0.01).


2010 ◽  
Vol 03 (03) ◽  
pp. 197-200 ◽  
Author(s):  
CHUNJIAO ZHOU ◽  
PENGFEI RONG ◽  
WENJIE ZHANG ◽  
JIANDA ZHOU ◽  
QINGLIN ZHANG ◽  
...  

Fulvic acid coated Fe 3 O 4 superparamagnetic nanoparticles were synthesized by a coprecipitation technique with iron salts and a small molecule stabilizer-fulvic acid. The prepared nanoparticles were well dispersed in water with about 10 nm in size according to transmission electron microscopy (TEM) observations. Fourier transform infrared spectroscopy (FTIR) revealed that fulvic acid were successfully covalently bonded to Fe 3 O 4 through the two adjacent phenolic hydroxyl groups and the carboxyl (- COOH ) groups were functionalized to the surface. The vibrating sample magnetometer (VSM) result showed that the nanoparticles were superparamagnetic and the saturation magnetizations were 60 emu/g. Moreover, their efficacy of liver magnetic resonance imaging (MRI) contrast agent was investigated by using live rat and tumor-bearing rabbit models through conventional clinical 1.5T MRI.


2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Yu-I Hsu ◽  
Atsushi Mahara ◽  
Tetsuji Yamaoka

For a water-soluble polyethylene glycol (PEG) magnetic resonance imaging (MRI) contrast agent, it has been demonstrated that the contrast efficiency was increased with increased branched structure of the contrast agent. However, the cause of enhanced contrast efficiency by the branched structure has not been clarified. Hence, we investigate the cause of the contrast agent enhancement by changing the Gd introduction ratio of the eight-arm PEG from 1.97 to 4.07; furthermore, the terminal mobility of the contrast agents with different structures was evaluated using proton nuclear magnetic resonance (1H-NMR) spectroscopy. It was shown that the relaxivity and contrast luminance of the synthesized branched PEG-Gd contrast agents are larger than those of linear PEG-Gd and commercially available contrast agents. Additionally, the change in the Gd introduction ratio did not affect the contrast efficiency. The terminal mobility results measured by NMR show that the linewidth at half height became broader with an increased number of branches, implying that the mobility of branched PEG-Gd is slower than that of linear PEG-Gd. Interestingly, the linewidth at half height of different structures did not change in an organic solvent; this phenomenon appeared specifically in water. It is suggested that the stable branched structure enabled the improvement in the relaxivity and contrast luminance.


2016 ◽  
Vol 7 (14) ◽  
pp. 2531-2541 ◽  
Author(s):  
Chunhua Guo ◽  
Ling Sun ◽  
Wenchuan She ◽  
Ning Li ◽  
Lei Jiang ◽  
...  

An amphiphilic dendronized heparin–gadolinium conjugate self-assembles into a nanoscale system by a combination of the features of the nanoparticle, dendrimer and heparin. The nanoscale system demonstrates great potential as an efficient and safe MRI contrast agent.


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