Development of a Molecular Probe for Detecting Cholinesterase Activity in MRI

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Researchers at the Massachusetts Institute of Technology have developed a new imaging probe called ChERT, which allows for the detection of cholinesterase (ChE) activity in the brain and peripheral regions using magnetic resonance imaging (MRI). This breakthrough could be crucial for studying the basic biology of cholinergic systems and disorders that affect their function. The study was funded by the HHS | National Institutes of Health and the G. Harold and Leila Y. Mathers Foundation. The research, published in the Proceedings of the National Academy of Sciences, demonstrated the effectiveness of ChERT in detecting ChE activity in both the brain and gut.

Key Takeaways:

  • The ChERT 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, confirming their specificity.
  • The probe labels regions of the gut where ChE expression is expected, and 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 study used wide-field brain delivery and abdominal delivery to demonstrate the effectiveness of ChERT in detecting ChE activity in different regions of the body.
  • The research was funded by the HHS | National Institutes of Health and the G. Harold and Leila Y. Mathers Foundation.
  • The study included a team of researchers from the Massachusetts Institute of Technology, including Miranda Dawson, Sajal Sen, Gregory D. Thiabaud, Kyle Backman, Itay Fayer, Sayani Das, Eliza Whitmire, Catherine Kung, Ali Barandov and Alan Jasanoff.

Statistics:

  • The study was published in the Proceedings of the National Academy of Sciences in 2025, specifically in volume 122, issue 41.
  • The research received funding from the HHS | National Institutes of Health and the G. Harold and Leila Y. Mathers Foundation.
  • The study used a wide-field brain delivery and abdominal delivery method to demonstrate the effectiveness of ChERT.
  • The ChERT probe underwent enzymatic processing, which reduced its solubility, promoting accumulation near sites of cholinesterase activity.

Sources:

  • Proceedings of the National Academy of Sciences, 2025;122(41).
  • Natl Acad Sciences, 2101 Constitution Ave NW, Washington, DC 20418, USA.
  • Miranda Dawson, Dept. of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • 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.