Triazoles as T₂‐Exchange Magnetic Resonance Imaging Contrast Agents for the Detection of Nitrilase Activity

Abstract

We characterized the T -exchange (T ) magnetic resonance imaging (MRI) contrast of azole protons that have large chemical shifts from the water proton resonance as a function of pH, temperature, and chemical modification. Our results showed that 1,2,4-triazoles could be tuned into excellent diamagnetic T contrast agents, with an optimal exchange-based relaxivity r of 0.10 s mm at physiological pH and B =9.4 T. A fit of r data to the Swift-Connick equation indicated that imino proton exchange of triazoles is dominated by a base-catalyzed process at higher pH values and an acid-catalyzed process at lower pH. The magnitude of r was also found to be heavily dependent on chemical modifications, that is, enhanced by electron-donating groups, such as amines and methyls, or by intramolecular hydrogen bonding between the imino proton and the carboxyl, and weakened by electron-withdrawing groups like bromo, cyano, and nitro. In light of these findings, we applied T MRI to assess the activity of nitrilase, an enzyme catalyzing the hydrolysis of 1,2,4-triazole-3-carbonitrile to 1,2,4-triazole-3-carboxylic acid, resulting in the enhancement of R . Our findings suggest that 1,2,4-triazoles have potential to provide sensitive and tunable diagnostic probes for MRI.

Highly efficient magnetic labelling allows MRI tracking of the homing of stem cell‐derived extracellular vesicles following systemic delivery

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Extradomain-B Fibronectin-Targeted Dextran-Based Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Probe for Detecting Pancreatic Cancer

“…Interestingly, T 2 relaxation times in the tumors consistently decreased ( p = 0.0067, two-tailed paired Student’s t test). As it is well-known that fast exchangeable protons including hydroxyl protons can also generate T 2ex MRI contrast, , the significant decrease in T 2 values further confirms the accumulation of Dex10-ZD2 in the tumors. Taken together, our results clearly demonstrated the capability of tumor imaging by targeting the overexpressed EDB-FN using Dex10-ZD2.…”

L‐glutamine as a T2 exchange contrast agent

“…It is important to note that the R 2ex also depends on the temperature and the magnetic field at which the relaxivity was measured. Some diamagnetic molecules appeared in the literature include D‐glucose (0.06 s −1 mM −1 at 7T, 22°C), 8 iopamidol (0.07 s −1 mM −1 at 7T, 37°C), 10 D‐maltose (0.08 s −1 mM −1 at 7T, 37°C), mannitol (0.024 s −1 mM −1 at 7T, 37°C), 9 phenols (0.017–0.059 s −1 mM −1 at 9.4T, 37°C), 26 and triazoles (0.10 s −1 mM −1 at 9.4T, 37°C) 27 . The measured R 2ex of the glutamine solution (Figure 2C) is also lower than that of other metal‐based T 2 contrast agents.…”