Enzyme-responsive PARACEST MRI contrast agents: A new biomedical imaging approach for studies of the proteasome

Byunghee Yoo, Manu S. Raam, Rachel M. Rosenblum, Mark D. Pagel

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

Proteases are important biomarkers for many biological processes and are popular targets for therapeutics investigations. A protease can be detected by monitoring changes in the paramagnetic chemical exchange saturation transfer (PARACEST) effect of a MRI contrast agent that serves as a substrate for the protease. To translate this type of responsive PARACEST MRI contrast agent to in vivo applications, the sensitivity, timing, specificity and validation of the response of the agent must be evaluated. This report demonstrates that PARACEST MRI contrast agents can be used to detect nanomolar concentrations of proteases, can be designed to preferentially detect the protease caspase-3 relative to caspase-8, and can be detected within the 15min time frame of typical MRI studies. The response can be validated using an unresponsive PARACEST MRI contrast agent as a control. A survey of the MEROPS database shows that this approach may also be applied to detect other proteases, and therefore may represent a new platform technology for studies of the proteasome.

Original languageEnglish (US)
Pages (from-to)189-198
Number of pages10
JournalContrast Media and Molecular Imaging
Volume2
Issue number4
DOIs
StatePublished - Jul 1 2007

Keywords

  • Enzyme kinetics
  • MRI
  • Molecular imaging
  • PARACEST
  • Protease
  • Proteasome

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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