A Novel pH‐Sensitive MRI Contrast Agent

Zhang, Shanrong; Wu, Kaigui; Sherry, A. Dean

doi:10.1002/(sici)1521-3773(19991102)38:21<3192::aid-anie3192>3.0.co;2-#

Cited by 234 publications

(75 citation statements)

References 11 publications

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“…1 MR probes capable of detecting specific biological events, including changes in pH, 2,3 ion concentration, 4–6 and the activity of enzymes 7 have been developed to expand MRI’s capabilities. Responsive MR agents are often based on modulating magnetic effects on the 1 H nuclei of water.…”

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confidence: 99%

¹⁹F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape

et al. 2016

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Magnetic resonance imaging (MRI) is a noninvasive imaging modality that provides excellent spatial and temporal resolution. The most commonly used MR probes face significant challenges originating from the endogenous 1H background signal of water. In contrast, fluorine MRI (19F MRI) allows quantitative probe imaging with zero background signal. Probes with high fluorine content are required for high sensitivity, suggesting nanoscale supramolecular assemblies containing 19F probes offer a potentially useful strategy for optimum imaging as a result of improved payload. We report here on supramolecular nanostructures formed by fluorinated peptide amphiphiles containing either glutamic acid or lysine residues in their sequence. We identified molecules that form aggregates in water which transition from cylindrical to ribbon-like shape as pH increased from 4.5 to 8.0. Interestingly, we found that ribbon-like nanostructures had reduced magnetic resonance signal, whereas their cylindrical counterparts exhibited strong signals. We attribute this drastic difference to the greater mobility of fluorinated tails in the hydrophobic compartment of cylindrical nanostructures compared to lower mobility in ribbon-like assemblies. This discovery identifies a strategy to design supramolecular, self-assembling contrast agents for 19F MRI that can spatially map physiologically relevant changes in pH using changes in morphology.

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confidence: 99%

¹⁹F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape

et al. 2016

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“…The number of coordinated water molecules, q , was determined using the method developed by Horrocks and coworkers. 8 …”

Section: Methodsmentioning

confidence: 99%

A (Fluoroalkyl)Guanidine Modulates the Relaxivity of a Phosphonate-Containing T 1 -Shortening Contrast Agent

Dawsey

Siriwardena-Mahanama

et al. 2014

Journal of Fluorine Chemistry

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Responsive magnetic resonance imaging (MRI) contrast agents, those that change their relaxivity according to environmental stimuli, have promise as next generation imaging probes in medicine. While several of these are known based on covalent modification of the contrast agents, fewer are known based on controlling non-covalent interactions. We demonstrate here accentuated relaxivity of a T1-shortening contrast agent, Gd-DOTP5− based on non-covalent, hydrogen bonding of Gd-DOTP5− with a novel fluorous amphiphile. By contrast to the phosphonate-containing Gd-DOTP5− system, the relaxivity of the analogous clinically approved contrast agent, Gd-DOTA− is unaffected by the same fluorous amphiphile under similar conditions. Mechanistic studies show that placing the fluorous amphiphile in proximity of the gadolinium center in Gd-DOTP5− caused an increase in τm (bound-water residence lifetime or the inverse of water exchange rate, τm = 1/kex) and an increase in τR (rotational correlation time), with τR being the factor driving enhanced relaxivity. Further, these effects were not observed when Gd-DOTA− was treated with the same fluorous amphiphile. Thus, Gd-DOTP5− and Gd-DOTA− respond to the fluorous amphiphile differently, presumably because the former binds to the amphiphile with higher affinity. (DOTP = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraphosphonic acid; DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid).

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“…Raghunand and co-workers monitored the time-dependent distribution of 28 and 29 (Figure 32) after sequential tail-vein injections. 31 Previously, Sherry and co-workers had demonstrated the pH-dependency of the r 1 of 28 , 13 where the hydrogen-bonding network of the pendant arms was influenced by changes in protonation state. Interestingly, 29 is pH-insensitive despite some structural similarities with 28 .…”

Section: Strategies For Concentration-independencementioning

confidence: 99%

“…Since these seminal reports, many other responsive contrast agents for MRI have been developed that respond to a wide range of stimuli including changes in pH, 13–33 temperature, 32–37 metal ion concentration, 12,38–40 and redox-active species. 41–48 Many responsive contrast agents are designed with the goal of improving diagnostic capabilities in vivo .…”

Section: Introductionmentioning

confidence: 99%

Overcoming the concentration-dependence of responsive probes for magnetic resonance imaging

Ekanger

Allen

2015

Metallomics

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In magnetic resonance imaging, contrast agents are molecules that increase the contrast-to-noise ratio of non-invasively acquired images. The information gained from magnetic resonance imaging can be increased using responsive contrast agents that undergo chemical changes, and consequently changes to contrast enhancement, for example in response to specific biomarkers that are indicative of diseases. A major limitation with modern responsive contrast agents is concentration-dependence that requires the concentration of contrast agent to be known: an extremely challenging task in vivo. Here, we review advances in several strategies aimed at overcoming the concentration-dependent nature of responsive contrast agents.

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A Novel pH‐Sensitive MRI Contrast Agent

Cited by 234 publications

References 11 publications

¹⁹F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape

¹⁹F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape

A (Fluoroalkyl)Guanidine Modulates the Relaxivity of a Phosphonate-Containing T 1 -Shortening Contrast Agent

Overcoming the concentration-dependence of responsive probes for magnetic resonance imaging

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A Novel pH‐Sensitive MRI Contrast Agent

Cited by 234 publications

References 11 publications

19F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape

19F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape

A (Fluoroalkyl)Guanidine Modulates the Relaxivity of a Phosphonate-Containing T 1 -Shortening Contrast Agent

Overcoming the concentration-dependence of responsive probes for magnetic resonance imaging

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¹⁹F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape

¹⁹F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape