A paramagnetic chemical exchange-based MRI probe metabolized by cathepsin D: design, synthesis and cellular uptake studies

Org Biomol Chem. 2010 Jun 7;8(11):2560-6. doi: 10.1039/b926639a. Epub 2010 Mar 26.

Abstract

Overexpression of the aspartyl protease cathepsin D is associated with certain cancers and Alzheimer's disease; thus, it is a potentially useful imaging biomarker for disease. A dual fluorescence/MRI probe for the potential detection of localized cathepsin D activity has been synthesized. The probe design includes both MRI and optical reporter groups connected to a cell penetrating peptide by a cathepsin D cleavable sequence. This design results in the selective intracellular deposition (determined fluorimetrically) of the MRI and optical reporter groups in the presence of overexpressed cathepsin D. The probe also provided clearly detectable in vitro MRI contrast by the mechanism of paramagnetic chemical exchange effects (OPARACHEE).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carboxylic Acids / chemistry
  • Cathepsin D / chemistry*
  • Cells, Cultured
  • Electron Spin Resonance Spectroscopy
  • Fluorescent Dyes / chemistry*
  • Humans
  • Magnetic Resonance Imaging
  • Molecular Structure

Substances

  • Carboxylic Acids
  • Fluorescent Dyes
  • Oregon Green 488 carboxylic acid
  • Cathepsin D