New calcium-selective smart contrast agents for magnetic resonance imaging

Area of Science:

• Neuroscience
• Biochemistry
• Medical Imaging

Background:

• Calcium homeostasis is critical for neuronal function; its dysregulation causes brain damage.
• Noninvasive monitoring of brain calcium (Ca2+) levels is essential for neurological research.

Purpose of the Study:

• To synthesize and characterize novel Ca2+-sensitive contrast agents (CAs) for magnetic resonance imaging (MRI) of brain extracellular fluid.
• To assess the selectivity, sensitivity, and relaxivity of the new CAs for Ca2+.

Main Methods:

• Synthesis of Gd(3+)-DO3A-APTRA based CAs.
• Evaluation of Ca2+ selectivity in buffer and physiological fluids.
• Relaxivity measurements upon Ca2+ addition.
• Characterization using luminescence lifetime, NMRD, and (17)O NMR experiments.

Main Results:

• The CAs demonstrated high selectivity for Ca2+ over other ions.
• A significant increase in relaxivity (100-157%) was observed upon Ca2+ binding, the highest for T1-based CAs.
• Analysis confirmed increased hydration state and slowed molecular rotation contribute to relaxivity enhancement.

Conclusions:

• The developed CAs are effective tools for noninvasively imaging Ca2+ dynamics in the brain.
• These agents can help study neurological conditions linked to calcium imbalance.
• The findings represent a significant advancement in MRI-based neuroimaging agents.