Europium(III) DOTA-tetraamide Complexes as Redox-Active MRI Sensors

Ratnakar, S. James; Viswanathan, Subha; Kovács, Zoltán; Jindal, Ashish; Green, Kayla N.; Sherry, A. Dean

doi:10.1021/ja211601k

Cited by 100 publications

(103 citation statements)

References 18 publications

(47 reference statements)

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“…Based on this result, a biocompatible PARACEST redox sensor was developed by mimicking one of the most important biological redox systems, the NADH/NAD + couple. [58] Eu 3+ - 16 , containing two N -methylquinolinium moieties as redox-active functional groups, [59] was nearly MRI silent in its oxidized form, but was turned on after reduction to the dihydroquinoline derivative by NADH (Figure 16). The larger CEST signal upon reduction arose from the slower, more optimal water exchange rate of the reduced form ( τ M = 90 μs).…”

Section: Introductionmentioning

confidence: 99%

Redox‐ and Hypoxia‐Responsive MRI Contrast Agents

et al. 2014

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The development of responsive or “smart” magnetic resonance imaging (MRI) contrast agents that can report specific biomarker or biological events has been the focus of MRI contrast agent research over the past 20 years. Among various biological hallmarks of interest, tissue redox and hypoxia are particularly important owing to their roles in disease states and metabolic consequences. Herein we review the development of redox-/hypoxia-sensitive T1 shortening and paramagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agents. Traditionally, the relaxivity of redox-sensitive Gd3+-based complexes is modulated through changes in the ligand structure or molecular rotation, while PARACEST sensors exploit the sensitivity of the metal-bound water exchange rate to electronic effects of the ligand-pendant arms and alterations in the coordination geometry. Newer designs involve complexes of redox-active metal ions in which the oxidation states have different magnetic properties. The challenges of translating redox- and hypoxia-sensitive agents in vivo are also addressed.

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Section: Introductionmentioning

confidence: 99%

Redox‐ and Hypoxia‐Responsive MRI Contrast Agents

et al. 2014

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“…In order to measure ROS, several methods have been developed including optical redox scanning 15 and exogenous contrast magnetic resonance imaging (MRI)-based methods. [16][17][18][19][20][21] Optical redox scanning acquires ex vivo fluorescence images from endogenous reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp) in order to map the tissue redox state that is related to ROS-induced oxidative stress. 15 However, this technique is invasive and only applicable to ex vivo tissues.…”

mentioning

confidence: 99%

“…Other MRI methods under development also rely on exogenous contrast agents with paramagnetic metallic ions (eg, Gd 31 and Eu 31 ). [19][20][21] Nevertheless, ideal ROS imaging should be endogenous and able to determine their changes in vivo with high spatial resolution and sensitivity.…”

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confidence: 99%

Imaging short‐lived reactive oxygen species (ROS) with endogenous contrast MRI

Tain

Scotti

et al. 2017

Magnetic Resonance Imaging

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Purpose: To characterize the relaxation properties of reactive oxygen species (ROS) for the development of endogenous ROS contrast magnetic resonance imaging (MRI). Materials and Methods: ROS-producing phantoms and animal models were imaged at 9.4T MRI to obtain T 1 and T 2 maps. Egg white samples treated with varied concentrations of hydrogen peroxide (H 2 O 2 ) were used to evaluate the effect of produced ROS in T 1 and T 2 for up to 4 hours. pH and temperature changes due to H 2 O 2 treatment in egg white were also monitored. The influences from H 2 O 2 itself and oxygen were evaluated in bovine serum albumin (BSA) solution producing no ROS. In addition, dynamic temporal changes of T 1 in H 2 O 2 -treated egg white samples were used to estimate ROS concentration over time and hence the detection sensitivity of relaxation-based endogenous ROS MRI. The relaxivity of ROS was compared with that of Gd-DTPA as a reference. Finally, the feasibility of in vivo ROS MRI with T 1 mapping acquired using an inversion recovery sequence was demonstrated with a well-established rotenone-treated mouse model (n 5 6). Results: pH and temperature changes in treated egg white samples were insignificant (<0.1 unit and <18C, respectively). T 1 relaxation time in the H 2 O 2 -treated egg white was reduced significantly (P < 0.05), while there was only small reduction in T 2 (<10%). In the H 2 O 2 -treated BSA solution that produce no ROS, there was a small change in T 1 due to H 2 O 2 itself (61%), although a significant T 2 -shortening effect was observed (>10%, P < 0.05). Also, there was a small reduction in T 1 (13 6 1%) and T 2 (1 6 2%) from molecular oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T 1 relaxivity of ROS was found to be much higher than that of Gd-DTPA (3.4 3 10 7 vs. 0.9 s 21 ÁmM 21 ). Finally, significantly reduced T 1 was observed in rotenone-treated mouse brain (5.1 6 2.5%, P < 0.05). Conclusion: We demonstrated in the study that endogenous ROS MRI based on the paramagnetic effect has sensitivity for in vitro and in vivo applications. Level of Evidence: 2 Technical Efficacy Stage: 2 J. MAGN. RESON. IMAGING 2018;47:222-229. R eactive oxygen species (ROS), including singlet oxygen, and hydroxyl radical (ÁOH), have long been subjects of study due to their central role in cell signaling, the aging process, and in the pathogenesis of a variety of diseases such as cardiovascular diseases, diabetes, cancer, Alzheimer's, and Parkinson's diseases. 1-5 ROS can be divided into radical species (eg, ÁOH) and nonradical species (eg, H 2 O 2 ). They are mainly produced by several different enzyme systems (eg, cytosolic enzyme) and by the mitochondrial complex I and III. 6 They can react readily with any surrounding tissue component (eg, lipids, proteins, and DNA) 2 and can initiate complicated chain processes with high biological impact (eg, Haber-Weiss or Fenton reactions). 7 The high reactivity and short lifetime of radical ROS make them very challenging to detect. For example, the lifetime...

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“…49,52,53 Although very few contrast agents directly responsive to ROS have been developed to date, interest in redox responsive probes and non-invasive methods of imaging the inflammatory process are emerging areas. 48,51,[54][55][56][57][58][59][60][61][62][63][64][65] One contrast agent that has been used successfully in numerous studies does so by responding to the presence of myeloperoxidase (MPO), a key biomarker for inflammation, and hydrogen peroxide. 54 Initial studies focused on 19 in which the active site was covalently linked to serotonin.…”

Section: Detection Of Nitric Oxidementioning

confidence: 99%

New reagents for detecting free radicals and oxidative stress

Olia

Schiesser

Taylor³

2014

Org. Biomol. Chem.

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Free radicals and oxidative stress play important roles in the deterioration of materials, and free radicals are important intermediates in many biological processes. The ability to detect these reactive species is a key step on the road to their understanding and ultimate control. This short review highlights recent progress in the development of reagents for the detection of free radicals and reactive oxygen species with broad application to materials science as well as biology.

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Europium(III) DOTA-tetraamide Complexes as Redox-Active MRI Sensors

Cited by 100 publications

References 18 publications

Redox‐ and Hypoxia‐Responsive MRI Contrast Agents

Redox‐ and Hypoxia‐Responsive MRI Contrast Agents

Imaging short‐lived reactive oxygen species (ROS) with endogenous contrast MRI

New reagents for detecting free radicals and oxidative stress

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