scholarly journals Genetic encoding of targeted MRI contrast agents for in vivo tumor imaging

2019 ◽  
Author(s):  
Simone Schuerle ◽  
Maiko Furubayashi ◽  
Ava P. Soleimany ◽  
Tinotenda Gwisai ◽  
Wei Huang ◽  
...  

AbstractTumor-selective contrast agents have the potential to aid in the diagnosis and treatment of cancer using noninvasive imaging modalities such as magnetic resonance imaging (MRI). Such contrast agents can consist of magnetic nanoparticles incorporating functionalities that respond to cues specific to tumor environments. Genetically engineering magnetotactic bacteria to display peptides has been investigated as a means to produce contrast agents that combine the robust image contrast effects of magnetosomes with transgenic targeting peptides displayed on their surface. This work reports the first use of magnetic nanoparticles that display genetically-encoded pH low insertion peptide (pHLIP), a long peptide intended to enhance MRI contrast by targeting the extracellular acidity associated with the tumors. To demonstrate the modularity of this versatile platform to incorporate diverse targeting ligands by genetic engineering, we also incorporated the cyclic αv integrin-binding peptide iRGD into separate magnetosomes. Specifically, we investigate their potential for enhanced binding and tumor imaging both in vitro and in vivo. Our experiments indicate that these tailored magnetosomes retain their magnetic properties, making them well-suited as T2 contrast agents, while exhibiting increased binding compared to wild-type magnetosomes.

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.


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.


Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 889 ◽  
Author(s):  
Nina Kostevšek ◽  
Calvin C. L. Cheung ◽  
Igor Serša ◽  
Mateja Erdani Kreft ◽  
Ilaria Monaco ◽  
...  

The majority of the clinically approved iron oxide nanoparticles (IO NPs) used as contrast agents for magnetic resonance imaging (MRI) have been withdrawn from the market either due to safety concerns or lack of profits. To address this challenge, liposomes have been used to prepare IO-based T2 contrast agents. We studied the influence of different phospholipids on the relaxivity (r2) values of magneto-liposomes (MLs) containing magnetic NPs in the bilayer, where a strong correlation between the bilayer fluidity and r2 is clearly shown. Embedding 5-nm IO NPs in the lipid bilayer leads to a significant improvement in their relaxivity, where r2 values range from 153 ± 5 s−1 mM−1 for DPPC/cholesterol/DSPE-PEG (96/50/4) up to 673 ± 12 s−1 mM−1 for DOPC/DSPE-PEG (96/4), compared to “free” IO NPs with an r2 value of 16 s−1 mM−1, measured at 9.4 T MRI scanner. In vitro MRI measurements, together with the ICP-MS analysis, revealed MLs as highly selective contrast agents that were preferentially taken up by cancerous T24 cells, which led to an improvement in the contrast and an easier distinction between the healthy and the cancerous cells. A careful selection of the lipid bilayer to prepare MLs could offer efficient MRI contrast agents, even at very low IO NP concentrations.


Sensors ◽  
2015 ◽  
Vol 15 (12) ◽  
pp. 31973-31986 ◽  
Author(s):  
Yuka Miyake ◽  
Syungo Ishikawa ◽  
Yu Kimura ◽  
Aoi Son ◽  
Hirohiko Imai ◽  
...  

Author(s):  
Brigit den Adel ◽  
Mat J. Daemen ◽  
Robert E. Poelmann ◽  
Louise van der Weerd

Recent advances in molecular resonance imaging of atherosclerosis enable to visualize atherosclerotic plaques in vivo using molecular targeted contrast agents. This offers opportunities to study atherosclerosis development and plaque vulnerability noninvasively. In this review, we discuss MRI contrast agents targeted toward atherosclerotic plaques and illustrate how these new imaging platforms could assist in our understanding of atherogenesis and atheroprogression. In particular, we highlight the challenges and limitations of the different contrast agents and hurdles for clinical application. We describe the most promising existing compounds to detect atherosclerosis and plaque vulnerability. Of particular interest are the fibrin-targeted compounds that detect thrombi and, furthermore, the contrast agents targeted to integrins that allow to visualize plaque neovascularization. Moreover, vascular cell adhesion molecule 1–targeted iron oxides seem promising for early detection of atherosclerosis. These targeted MRI contrast agents, however promising and well characterized in (pre)clinical models, lack specificity for plaque vulnerability.


Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1355
Author(s):  
Shanti Marasini ◽  
Huan Yue ◽  
Son Long Ho ◽  
Ji Ae Park ◽  
Soyeon Kim ◽  
...  

Polyacrylic acid (PAA)-coated lanthanide oxide (Ln2O3) nanoparticles (NPs) (Ln = Tb and Ho) with high colloidal stability and good biocompatibility were synthesized, characterized, and investigated as a new class of negative (T2) magnetic resonance imaging (MRI) contrast agents at high MR fields. Their r2 values were appreciable at a 3.0 T MR field and higher at a 9.4 T MR field, whereas their r1 values were negligible at all MR fields, indicating their exclusive induction of T2 relaxations with negligible induction of T1 relaxations. Their effectiveness as T2 MRI contrast agents at high MR fields was confirmed from strong negative contrast enhancements in in vivo T2 MR images at a 9.4 T MR field after intravenous administration into mice tails.


2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Hyeona Yim ◽  
Seogjin Seo ◽  
Kun Na

Various imaging technologies have become increasingly important in developing a better understanding of information on the biological and clinical phenomena associated with diseases of interest. Of these technologies, magnetic resonance imaging (MRI) is one of the most powerful for clinical diagnosis and in vivo imaging without the exposure to ionising radiation or radiotracers. Despite its many advantages, there are intrinsic limitations caused by MRI contrast agents, such as short vascular half-life circulation, which lead to unwanted side effects. In this review, we will focus on the multifunctional modification of MRI contrast agents for diagnosis and therapy.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
V. Naumenko ◽  
A. Garanina ◽  
A. Nikitin ◽  
S. Vodopyanov ◽  
N. Vorobyeva ◽  
...  

Magnetic resonance imaging (MRI) is a powerful technique for tumor diagnostics. Iron oxide nanoparticles (IONPs) are safe and biocompatible tools that can be used for further enhancing MR tumor contrasting. Although numerous IONPs have been proposed as MRI contrast agents, low delivery rates to tumor site limit its application. IONPs accumulation in malignancies depends on both IONPs characteristics and tumor properties. In the current paper, three differently shaped Pluronic F-127-modified IONPs (nanocubes, nanoclusters, and nanorods) were compared side by side in three murine tumor models (4T1 breast cancer, B16 melanoma, and CT26 colon cancer). Orthotopic B16 tumors demonstrated more efficient IONPs uptake than heterotopic implants. Magnetic nanocubes (MNCb) had the highest r2-relaxivity in vitro (300 mM−1·s−1) compared with magnetic nanoclusters (MNCl, 104 mM−1·s−1) and magnetic nanorods (MNRd, 51 mM−1·s−1). As measured by atomic emission spectroscopy, MNCb also demonstrated better delivery efficiency to tumors (3.79% ID) than MNCl (2.94% ID) and MNRd (1.21% ID). Nevertheless, MNCl overperformed its counterparts in tumor imaging, providing contrast enhancement in 96% of studied malignancies, whereas MNCb and MNRd were detected by MRI in 73% and 63% of tumors, respectively. Maximum MR contrasting efficiency for MNCb and MNCl was around 6-24 hours after systemic administration, whereas for MNRd maximum contrast enhancement was found within first 30 minutes upon treatment. Presumably, MNRd poor MRI performance was due to low r2-relaxivity and rapid clearance by lungs (17.3% ID) immediately after injection. MNCb and MNCl were mainly captured by the liver and spleen without significant accumulation in the lungs, kidneys, and heart. High biocompatibility and profound accumulation in tumor tissues make MNCb and MNCl the promising platforms for MRI-based tumor diagnostics and drug delivery.


2017 ◽  
Vol 3 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Chris J. Zhang ◽  
Michael S. Valic ◽  
Juan Chen ◽  
Gang Zheng

Porphysome nanoparticles are composed of porphyrin-conjugated lipids. The attachment of the porphyrin moiety to each phospholipid confers novel properties to the liposome-like nanoparticle, allowing it to perform a variety of diagnostic and therapeutic applications. The metal chelating properties of porphyrin can be used to bind manganese (Mn), transforming the porphysome into a contrast agent for magnetic resonance imaging (MRI). Previous work has extensively characterized the properties of the Mn-porphysome. Herein, we build upon that work by demonstrating the bio-interactions of Mn-porphysomes in vitro to validate their study in vivo. Particle stability in serum was inferred from fluorescence quenching efficiency, and tolerability to cells was measured using an MTT assay. Mn-porphysomes remained >80% quenched after 14H and showed no toxicity to cells at concentrations below 125 mM. These preliminary results suggest that the porphysome may be used to enhance MRI contrast in vivo.


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