A paramagnetic chemical exchange-based MRI probe metabolized by cathepsin D: design, synthesis and cellular uptake studies.
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).
Suchý
Mojmír
M
Department of Chemistry, The University of Western Ontario, London, Ontario, Canada N6A 5B7.
Ta
Robert
R
Li
Alex X
AX
Wojciechowski
Filip
F
Pasternak
Stephen H
SH
Bartha
Robert
R
Hudson
Robert H E
RH
D002264:Carboxylic Acids / Q000737:chemistry; D002402:Cathepsin D / Q000737:chemistry*; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging; D015394:Molecular Structure
D002264:Carboxylic Acids; D005456:Fluorescent Dyes; C436864:Oregon Green 488 carboxylic acid; D002402:Cathepsin D