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Area of Science:

  • Biophysics
  • Molecular Imaging
  • Biochemistry

Background:

  • Genetically encoded contrast agents offer non-invasive biomarker detection in vivo.
  • Hyperpolarized 129Xe Nuclear Magnetic Resonance (NMR) techniques provide sensitive molecular imaging capabilities.

Purpose of the Study:

  • To develop and validate genetically encoded, analyte-sensitive molecular imaging agents.
  • To quantify maltose using a novel hyper-CEST 129Xe NMR approach with maltose binding protein (MBP).

Main Methods:

  • Utilized hyper-CEST 129Xe NMR to monitor xenon exchange with MBP.
  • Quantified maltose concentrations ranging from 32 nM to 1 mM.
  • Investigated MBP variants, including a Val to Ala mutation, for enhanced contrast properties.

Main Results:

  • MBP demonstrated ultrasensitive, "smart" contrast agent properties, with no signal in the absence of maltose.
  • Bound 129Xe showed a significant downfield shift (Δδ = 95 ppm), enabling detection in E. coli and multiplexing.
  • An MBP mutation enhanced contrast by 34% and shifted 129Xe resonance upfield by 59 ppm.

Conclusions:

  • Engineered MBPs represent a new class of genetically encoded, analyte-sensitive molecular imaging agents.
  • These agents are detectable by 129Xe NMR/MRI, opening avenues for sensitive biomarker detection.