Dataset Information

Hydrazone Molecular Switches with Paramagnetic Center as ¹⁹F Magnetic Resonance Imaging Relaxation Enhancement Agents for pH Imaging.

ABSTRACT: The design and synthesis of hydrazone-based switches with a CF₃ reporting group for ¹⁹F pH imaging using relaxation rate changes were described. A paramagnetic center was introduced into the hydrazone molecular switch scaffold by substitution of an ethyl functional group with a paramagnetic complex. The mechanism of activation relies on a gradual increase in T₁ and T₂ magnetic resonance imaging (MRI) relaxation times as pH decreases due to E/Z isomerization, which results in a change in the distance between fluorine atoms and the paramagnetic center. Among the three possible variants of the ligand, the meta isomer was found to offer the highest potential changes in relaxation rates due to the significant paramagnetic relaxation enhancement (PRE) effect and a stable position of the ¹⁹F signal, allowing for the tracking of a single narrow ¹⁹F resonance for imaging purposes. The selection of the most suitable Gd(III) paramagnetic ion for complexation was conducted by theoretical calculations based on the Bloch-Redfield-Wangsness (BRW) theory, taking into account the electron-nucleus dipole-dipole and Curie interactions only. The results were verified experimentally, confirming the accuracy of theoretical predictions, good solubility, and stability of the agents in water and the reversible transition between E and Z-H⁺ isomers. The results demonstrate the potential of this approach for pH imaging using relaxation rate changes instead of chemical shift.

SUBMITTER: Janasik D

PROVIDER: S-EPMC10226166 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hydrazone Molecular Switches with Paramagnetic Center as 19F Magnetic Resonance Imaging Relaxation Enhancement Agents for pH Imaging.

Janasik Dawid D Jasiński Krzysztof K Szreder Julia J Węglarz Władysław P WP Krawczyk Tomasz T

ACS sensors 20230517 5

The design and synthesis of hydrazone-based switches with a CF3 reporting group for 19F pH imaging using relaxation rate changes were described. A paramagnetic center was introduced into the hydrazone molecular switch scaffold by substitution of an ethyl functional group with a paramagnetic complex. The mechanism of activation relies on a gradual increase in T1 and T2 magnetic resonance imaging (MRI) relaxation times as pH decreases due t ...[more]

PMID: 37198734

Similar Datasets

Project description:Paramagnetic gadolinium ions (GdIII), complexed within DOTA-based chelates, have become useful tools to increase the magnetic resonance imaging (MRI) contrast in tissues of interest. Recently, "on/off" probes serving as 19F·MRI biosensors for target enzymes have emerged that utilize the increase in transverse (T 2 ∗ or T 2) relaxation times upon cleavage of the paramagnetic GdIII centre. Molecular 19F·MRI has the advantage of high specificity due to the lack of background signal but suffers from low signal intensity that leads to low spatial resolution and long recording times. In this work, an "on/off" probe concept is introduced that utilizes responsive deactivation of paramagnetic relaxation enhancement (PRE) to generate 19F longitudinal (T 1) relaxation contrast for accelerated molecular MRI. The probe concept is applied to matrix metalloproteinases (MMPs), a class of enzymes linked with many inflammatory diseases and cancer that modify bioactive extracellular substrates. The presence of these biomarkers in extracellular space makes MMPs an accessible target for responsive PRE deactivation probes. Responsive PRE deactivation in a 19F biosensor probe, selective for MMP-2 and MMP-9, is shown to enable molecular MRI contrast at significantly reduced experimental times compared to previous methods. PRE deactivation was caused by MMP through cleavage of a protease substrate that served as a linker between the fluorine-containing moiety and a paramagnetic GdIII-bound DOTA complex. Ultrashort echo time (UTE) MRI and, alternatively, short echo times in standard gradient echo (GE) MRI were employed to cope with the fast 19F transverse relaxation of the PRE active probe in its "on-state." Upon responsive PRE deactivation, the 19F·MRI signal from the "off-state" probe diminished, thereby indicating the presence of the target enzyme through the associated negative MRI contrast. Null point 1H·MRI, obtainable within a short time course, was employed to identify false-positive 19F·MRI responses caused by dilution of the contrast agent.

Dataset Information

Hydrazone Molecular Switches with Paramagnetic Center as ¹⁹F Magnetic Resonance Imaging Relaxation Enhancement Agents for pH Imaging.

Publications

Hydrazone Molecular Switches with Paramagnetic Center as <sup>19</sup>F Magnetic Resonance Imaging Relaxation Enhancement Agents for pH Imaging.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets