Peptide hydrogels generating chemical exchange saturation transfer MRI contrast and uses thereof
Inventors
McMahon, Michael T. • Chan, Kannie Wai-Yan • Giano, Michael Christopher • Oskolkov, Nikita • Schneider, Joel Patrick • Song, Xiaolei
Assignees
Johns Hopkins University • National Institutes of Health NIH • Kennedy Krieger Institute Inc
Publication Number
US-11235075-B2
Publication Date
2022-02-01
Expiration Date
2034-04-28
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Abstract
The present invention provides novel hydrogels through peptides, which are designed to self-assemble and produce magnetic resonance (MR) contrast through chemical exchange saturation transfer (CEST). The location and integrity of these gels could consequently be tracked using MR imaging. The self-assembly of the peptides into hydrogels can be brought about by a change in pH, ionic strength, temperature, and concentration of ions.
Core Innovation
The invention provides novel peptide-based hydrogels designed to self-assemble and produce magnetic resonance (MR) contrast through chemical exchange saturation transfer (CEST). These hydrogels can be tracked in location and integrity using MR imaging, taking advantage of the self-assembly properties of peptides triggered by changes in pH, ionic strength, temperature, and ion concentration.
The problem addressed is the limitations and safety concerns of current metal-based MR contrast agents, such as paramagnetic agents containing gadolinium and manganese, which require relatively high doses and may pose toxicity risks. These traditional agents also provide only one type of contrast and may have difficulties distinguishing contrast sources in images.
The invention aims to provide a non-metallic, biocompatible CEST contrast agent that produces multi-color MRI detection by using peptide-based hydrogels with exchangeable protons. These peptides contain amino acids such as lysine, arginine, serine, threonine, histidine, tryptophan, and unnatural amino acids with heterocyclic protons, generating suitable chemical shifts and exchange rates to produce CEST contrast and allowing real-time tracking of the gels in subjects.
Claims Coverage
The patent contains two independent claims that cover the composition of a peptide-based hydrogel as an MR contrast agent and a method of MR imaging using such agent. Each claim emphasizes the biochemical composition and functional properties of the hydrogel.
Peptide-based hydrogel MR contrast agent composition
The agent is a biocompatible chemical exchange saturation transfer (CEST) peptide-based hydrogel composed of two β-strands with alternating hydrophobic (valine) and hydrophilic residues (selected from histidine, serine, and aspartate) flanking a tetrapeptide turn sequence 'Val-pro-Pro-Thr'. The hydrogel inherently acts as a contrast agent configured to create detectable contrast via a CEST MR imaging method.
Method of MR imaging using peptide-based CEST hydrogel
A method comprising providing and delivering the peptide-based hydrogel agent described above to a subject and obtaining MR images using a chemical exchange saturation transfer (CEST) MR imaging technique.
The claims collectively cover the novel peptide hydrogel composition designed for CEST MR contrast and methods to utilize these hydrogels for enhanced MR imaging through selective contrast generation and detection using CEST.
Stated Advantages
Provides a non-metallic alternative to traditional metal-based MR contrast agents, potentially increasing safety by avoiding metal toxicity.
Enables multi-color MRI detection through peptides with different exchangeable protons allowing simultaneous tracking of multiple probes or drugs.
Biocompatible and biodegradable peptide hydrogels responsive to environmental changes like pH and ion concentration, allowing customized imaging applications.
Ability to monitor location and integrity of the hydrogels in vivo using CEST MR imaging.
Documented Applications
Use as MR contrast agents for in vivo imaging to track the location and integrity of peptide hydrogels.
MR imaging applications involving monitoring drug delivery particles, tissue characterization, and possibly tracking multiple agents simultaneously due to multi-frequency contrast.
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