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Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging
Published on: December 4, 2016
A paramagnetic chemical exchange-based MRI probe metabolized by cathepsin D: design, synthesis and cellular uptake
Mojmír Suchý1, Robert Ta, Alex X Li
1Department of Chemistry, The University of Western Ontario, London, Ontario, Canada N6A 5B7.
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).
Insights
A novel dual probe detects cathepsin D, an enzyme linked to cancer and Alzheimer's disease. This imaging tool shows promise for diagnosing diseases by visualizing enzyme activity.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Biochemistry
Background:
- Cathepsin D overexpression is linked to cancer and Alzheimer's disease.
- Cathepsin D is a potential imaging biomarker for disease detection.
- Targeting specific enzyme activity is crucial for accurate disease diagnosis.
Purpose of the Study:
- To synthesize a dual fluorescence/MRI probe for detecting localized cathepsin D activity.
- To develop a novel imaging biomarker for diseases associated with cathepsin D.
- To assess the probe's ability to selectively report cathepsin D activity in vitro.
Main Methods:
- Synthesized a dual fluorescence/MRI probe incorporating MRI and optical reporters.
- Linked reporters to a cell-penetrating peptide via a cathepsin D cleavable sequence.
- Utilized fluorimetry for intracellular deposition assessment and OPARACHEE for MRI contrast detection.
Main Results:
- The probe selectively deposited MRI and optical reporters intracellularly in the presence of overexpressed cathepsin D.
- Fluorimetric analysis confirmed selective intracellular deposition.
- The probe generated detectable in vitro MRI contrast via OPARACHEE.
Conclusions:
- The synthesized dual probe effectively detects cathepsin D activity.
- This probe demonstrates potential as an imaging biomarker for diseases like cancer and Alzheimer's.
- The probe's design enables selective detection and provides dual-mode imaging capabilities.
