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Related Experiment Video

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MMP-2/9-Specific Activatable Lifetime Imaging Agent.

Marcus T M Rood1, Marcel Raspe2, Jan Bart ten Hove3,4

  • 1Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden 2300RC, The Netherlands. m.t.m.rood@lumc.nl.

Sensors (Basel, Switzerland)
|May 19, 2015
PubMed
Summary

This study introduces a novel activatable lifetime imaging agent combining fluorescence and luminescence lifetime imaging. This dual-modality agent shows promise for developing future disease-specific imaging tools.

Keywords:
FRETMMPenzymatic activationfluorescenceiridiumlifetime imagingluminescence

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Area of Science:

  • Molecular imaging
  • Biomedical optics
  • Nanotechnology

Background:

  • Optical imaging benefits from combining high signal-to-background ratio of activatable fluorescence imaging with high specificity of luminescence lifetime imaging.
  • Integrating these techniques requires a sophisticated imaging agent design.

Purpose of the Study:

  • To develop and characterize a novel activatable lifetime imaging agent.
  • To demonstrate the feasibility of combining enzymatic signal activation with luminescence lifetime imaging.

Main Methods:

  • Designed an imaging agent with two luminophores (Ir(ppy)3 and Cy5) tethered by a peptide for proximity-induced quenching and enzymatic cleavage.
  • Investigated luminescence quenching and lifetime changes in vitro upon enzymatic cleavage by tumor-related MMP-2/9.
  • Used a Cy3-Cy5 pair as a reference for luminescence activation.

Main Results:

  • In close proximity, Cy5 quenched Ir(ppy)3 emission and shortened its luminescence lifetime from 98 ns to 30 ns.
  • Enzymatic cleavage restored Ir(ppy)3 and Cy5 luminescence and returned the Ir(ppy)3 lifetime to 94 ns.
  • Demonstrated successful signal activation and lifetime restoration in vitro.

Conclusions:

  • The combination of enzymatic signal activation with lifetime imaging is feasible.
  • This approach offers a promising strategy for designing future disease-specific imaging agents.
  • The developed activatable lifetime imaging agent shows potential for enhanced molecular imaging applications.