A molecular probe for detecting cholinesterase activity in MRI

Area of Science:

• Neuroscience
• Biomedical Imaging
• Molecular Biology

Background:

• Cholinesterase (ChE) enzymes are crucial for neurotransmission, regulating acetylcholine activity.
• Noninvasive monitoring of ChE activity is vital for understanding cholinergic systems and related disorders.
• Current methods for ChE detection lack noninvasive, whole-body applicability.

Purpose of the Study:

• To develop a novel imaging probe for noninvasive detection of cholinesterase activity using Magnetic Resonance Imaging (MRI).
• To assess the probe's ability to visualize ChE-rich regions in both the brain and peripheral tissues.
• To confirm the specificity and localization of the probe in relation to cholinesterase activity.

Main Methods:

• Development of a novel imaging probe, ChERT, designed to undergo enzymatic processing and reduced solubility for accumulation at ChE sites.
• Administration of ChERT via wide-field brain and abdominal delivery in animal models.
• Detection of ChERT-induced MRI contrast changes and confirmation using fluorescence microscopy and enzymatic inhibitors.

Main Results:

• ChERT successfully produced detectable MRI contrast changes in brain regions known for high cholinesterase enrichment.
• ChERT accumulation and MRI signal changes were suppressed by a selective enzymatic inhibitor, confirming probe specificity.
• Following abdominal delivery, ChERT effectively labeled peripheral tissues, specifically regions of the gut with expected ChE expression.
• Fluorescence microscopy confirmed colocalization of ChERT with ChE in both brain and peripheral tissues at higher resolution.

Conclusions:

• The developed ChERT probe enables noninvasive detection and visualization of cholinesterase activity using MRI.
• ChERT demonstrates versatility for assessing cholinergic phenotypes throughout the body, including the brain and periphery.
• This imaging agent offers a promising tool for basic research and clinical applications related to cholinergic systems.