Development of a Molecular Probe for Detecting Cholinesterase Activity in MRI

Strategic Insights -

Researchers at the Massachusetts Institute of Technology have developed a new imaging probe that allows for the noninvasive detection of cholinesterase (ChE) activity in the brain and periphery using magnetic resonance imaging (MRI). This breakthrough could be significant for studying the basic biology of cholinergic systems and disorders that affect their function. The probe, called ChERT, undergoes enzymatic processing that reduces its solubility, promoting accumulation near sites of cholinesterase activity. After wide-field brain delivery, ChERT produces MRI contrast changes in brain regions known to be enriched in cholinesterases, which are suppressed in the presence of a selective enzymatic inhibitor, confirming their specificity.

Key Takeaways:

  • The ChERT probe is a novel imaging agent that allows for the detection of cholinesterase activity in the brain and periphery using MRI.
  • The probe undergoes enzymatic processing that reduces its solubility, promoting accumulation near sites of cholinesterase activity.
  • ChERT produces MRI contrast changes in brain regions known to be enriched in cholinesterases, which are suppressed in the presence of a selective enzymatic inhibitor.
  • The probe was found to label regions of the gut where ChE expression is expected after abdominal delivery.
  • Colocalization of ChERT with ChE could be confirmed and visualized at higher resolution by fluorescence microscopy.
  • The ChERT agent provides a potentially versatile basis for assessment of cholinergic phenotypes throughout the body.
  • The research has been peer-reviewed and published in the Proceedings of the National Academy of Sciences.
  • The study was funded by the National Institutes of Health and the G. Harold and Leila Y. Mathers Foundation.
  • The research team included Miranda Dawson, Sajal Sen, Gregory D. Thiabaud, Kyle Backman, Itay Fayer, Sayani Das, Eliza Whitmire, Catherine Kung, Ali Barandov, and Alan Jasanoff.

Statistics:

  • 122(41) - Volume and issue number of the Proceedings of the National Academy of Sciences where the research was published.
  • 2101 Constitution Ave NW, Washington, DC 20418, USA - Address of the National Academy of Sciences.
  • 2025 - Year when the research was conducted and published.
  • October 21, 2025 - Date of publication of the news report by Life Science Weekly.
  • 1540 - Page number where the news report was published.

Sources:

  • A molecular probe for detecting cholinesterase activity in MRI. Proceedings of the National Academy of Sciences, 2025;122(41).
  • Natl Acad Sciences, 2101 Constitution Ave NW, Washington, DC 20418, USA - Publisher contact information for the journal Proceedings of the National Academy of Sciences.
  • NewsRx. Findings on Carboxylic Ester Hydrolases Reported by Researchers at Massachusetts Institute of Technology (A molecular probe for detecting cholinesterase activity in MRI). Life Science Weekly. October 21, 2025; p 1540.