A pH-Responsive MRI Agent that Can Be Activated Beyond the Tissue Magnetization Transfer Window

Area of Science:

• Medical imaging
• Biophysical chemistry
• Contrast agent development

Background:

• Magnetic Resonance Imaging (MRI) is a powerful tool for non-invasive tissue visualization.
• Current MRI techniques for pH measurement are limited by interference and require knowledge of contrast agent concentration.
• Developing new contrast agents is crucial for advancing MRI capabilities.

Purpose of the Study:

• To develop a novel terbium-based complex for direct pH measurement using MRI.
• To overcome the limitations of existing pH-sensitive MRI methods.
• To enable pH imaging independent of contrast agent concentration and tissue signals.

Main Methods:

• Synthesis and characterization of a terbium-based complex.
• Investigation of the complex's water exchange properties.
• Evaluation of the complex's performance in pH-dependent Chemical Exchange Saturation Transfer (CEST) MRI.
• Assessment of interference from biological background signals.

Main Results:

• The terbium-based complex exhibits a CEST resonance significantly shifted from typical tissue signals.
• Deprotonation of a phenolic proton causes a 56 ppm frequency shift in the bound water exchange peak within the pH range of 5-8.
• This shift allows for direct pH readout via MRI.
• The method demonstrates minimal interference from tissue Magnetization Transfer (MT) signals.

Conclusions:

• A terbium-based complex enables direct, accurate pH imaging using MRI.
• The agent's unique resonance properties circumvent the need for agent concentration determination.
• This approach offers a significant advancement for in vivo pH monitoring.