scholarly journals Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

2015 ◽  
Vol 112 (21) ◽  
pp. 6607-6612 ◽  
Author(s):  
Shenghui Xue ◽  
Hua Yang ◽  
Jingjuan Qiao ◽  
Fan Pu ◽  
Jie Jiang ◽  
...  

With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd3+ toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd3+ and a 1011-fold greater selectivity for Gd3+ over Zn2+ compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol−1⋅s−1/89.2 mmol−1⋅s−1 per particle). Using T1- and T2-weighted, as well as T2/T1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10–20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.

2021 ◽  
Vol 11 (3) ◽  
pp. 1165
Author(s):  
Wen-Tien Hsiao ◽  
Yi-Hong Chou ◽  
Jhong-Wei Tu ◽  
Ai-Yih Wang ◽  
Lu-Han Lai

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.


Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1235
Author(s):  
Xiaohui Nan ◽  
Wenjia Lai ◽  
Dan Li ◽  
Jiesheng Tian ◽  
Zhiyuan Hu ◽  
...  

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.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Christian E. Anderson ◽  
Mette Johansen ◽  
Bernadette O. Erokwu ◽  
He Hu ◽  
Yuning Gu ◽  
...  

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.


RSC Advances ◽  
2021 ◽  
Vol 11 (51) ◽  
pp. 32216-32226
Author(s):  
Ramesh Marasini ◽  
Sagar Rayamajhi ◽  
Anthony Moreno-Sanchez ◽  
Santosh Aryal

In pursuit of safer alternatives to Gd-based MRI contrast agents due to its toxicity and organ deposition, herein, we developed a safer and efficient clinically relevant iron(iii) chelated polymeric nanoparticle as a T1-weighted MRI contrast agent.


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Rami Tadros ◽  
Bhakti Rawal ◽  
Karen Briley-Saebo ◽  
David O’Connor ◽  
Dan Han ◽  
...  

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.


2020 ◽  
Vol 13 (10) ◽  
pp. 296
Author(s):  
Friederike Reeßing ◽  
Sèvrin E. M. Huijsse ◽  
Rudi A. J. O. Dierckx ◽  
Ben L. Feringa ◽  
Ronald J.H. Borra ◽  
...  

Thanks to its innocuousness and high spatiotemporal resolution, light is used in several established and emerging applications in biomedicine. Among them is the modulation of magnetic resonance imaging (MRI) contrast agents’ relaxivity with the aim to increase the sensitivity, selectivity and amount of functional information obtained from this outstanding whole-body medical imaging technique. This approach requires the development of molecular contrast agents that show high relaxivity and strongly pronounced photo-responsiveness. To this end, we report here the design and synthesis of a light-activated MRI contrast agent, together with its evaluation using UV–vis spectroscopy, Fast Field Cycling (FFC) relaxometry and relaxometric measurements on clinical MRI scanners. The high relaxivity of the reported agent changes substantially upon irradiation with light, showing a 17% decrease in relaxivity at 0.23T upon irradiation with λ = 400 nm (violet) light for 60 min. On clinical MRI scanners (1.5T and 3.0T), irradiation leads to a decrease in relaxivity of 9% and 19% after 3 and 60 min, respectively. The molecular design presents an important blueprint for the development of light-activatable MRI contrast agents.


2012 ◽  
Vol 70 (4) ◽  
pp. 1016-1025 ◽  
Author(s):  
Nevin McVicar ◽  
Alex X. Li ◽  
Mojmír Suchý ◽  
Robert H. E. Hudson ◽  
Ravi S. Menon ◽  
...  

2016 ◽  
Vol 7 (7) ◽  
pp. 4230-4236 ◽  
Author(s):  
Lyndsay M. Randolph ◽  
Clare L. M. LeGuyader ◽  
Michael E. Hahn ◽  
Christopher M. Andolina ◽  
Joseph P. Patterson ◽  
...  

A Gd3+-coordinated polymerizable analogue of the MRI contrast agent Gd-DOTA was used to prepare amphiphilic block copolymers, with hydrophilic blocks composed entirely of the polymerized contrast agent.


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