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

• Published in: Organic & biomolecular chemistry Vol. 8; no. 11; p. 2560
• Main Authors: Suchý, Mojmír, Ta, Robert, Li, Alex X, Wojciechowski, Filip, Pasternak, Stephen H, Bartha, Robert, Hudson, Robert H E
• Format: Journal Article
• Language: English
• Published: England 01-01-2010
• Subjects: Carboxylic Acids - chemistry; Cathepsin D - chemistry; Cells, Cultured; Electron Spin Resonance Spectroscopy; Fluorescent Dyes - chemistry; Humans; Magnetic Resonance Imaging; Molecular Structure
• ISSN: 1477-0539
• DOI: 10.1039/b926639a

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).