A Paramagnetic Chemical Exchange-based MRI Probe Metabolized by Cathepsin D: Design, Synthesis and Cellular Uptake Studies

Authors

Mojmír Suchý, The University of Western Ontario
Robert Ta, The University of Western Ontario
Alex X. Li, The University of Western Ontario
Filip Wojciechowski, The University of Western Ontario
Stephen H. Pasternak, The University of Western Ontario
Robert Bartha, The University of Western Ontario
Robert H. E. Hudson, The University of Western Ontario

Document Type

Article

Publication Date

6-7-2010

Journal

Organic & Biomolecular Chemistry

Volume

8

Issue

11

First Page

2560

Last Page

2566

URL with Digital Object Identifier

http://dx.doi.org/10.1039/b926639a

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).