Iron(II) PARACEST MRI contrast agents.

Area of Science:

• Inorganic Chemistry
• Magnetic Resonance Imaging
• Biomedical Engineering

Background:

• Paramagnetic chemical exchange saturation transfer (PARACEST) agents are crucial for enhancing MRI sensitivity.
• Developing novel PARACEST agents with improved stability and distinct chemical shifts is an ongoing research area.
• Iron(II) complexes offer potential as cost-effective and tunable PARACEST agents.

Purpose of the Study:

• To report the first examples of Fe(II)-based PARACEST magnetic resonance contrast agents.
• To synthesize and characterize novel iron(II) complexes with macrocyclic ligands (L1 and L2).
• To evaluate the CEST properties and imaging capabilities of these new Fe(II) PARACEST agents.

Main Methods:

• Synthesis of iron(II) complexes with macrocyclic ligands 1,4,7-tris(carbamoylmethyl)-1,4,7-triazacyclononane (L1) and 1,4,7-tris[(5-amino-6-methyl-2-pyridyl)methyl]-1,4,7-triazacyclononane (L2).
• Determination of formation constants and stability of Fe(II) complexes in aqueous solution.
• Characterization of exchangeable protons and their CEST peak positions using MRI.
• CEST imaging experiments in solutions at varying concentrations, pH, ionic strength, and temperatures.

Main Results:

• Stable Fe(II) complexes with macrocyclic ligands L1 and L2 were synthesized, exhibiting formation constants of log K = 13.5 and 19.2, respectively.
• The complexes maintain the Fe(II) state in the presence of air.
• Amide protons of [Fe(L1)](2+) showed a CEST peak at 69 ppm, while amino protons of [Fe(L2)](2+) exhibited a peak at 6 ppm downfield from water.
• Observable CEST effects were demonstrated in low millimolar concentrations under physiological conditions (pH 7, 100 mM NaCl, 20 mM buffer, 25 °C or 37 °C).

Conclusions:

• Novel Fe(II) PARACEST agents based on macrocyclic ligands have been successfully developed.
• These agents demonstrate distinct CEST peak shifts and are observable under relevant physiological conditions.
• The findings present promising new candidates for MRI contrast agents, particularly for Fe(II)-based PARACEST applications.