Peptide hydrogels generating chemical exchange saturation transfer MRI contrast and uses thereof
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.
1. An agent for use in conjunction with magnetic resonance (MR) imaging comprising:
a biocompatible chemical exchange saturation transfer (CEST) agent;
wherein said biocompatible CEST agent takes the form of a peptide-based hydrogel comprising two β-strands comprising alternating hydrophobic and hydrophilic residues flanking a tetrapeptide turn sequence, wherein the hydrophobic residues comprise valine, each hydrophilic residue is selected from a group consisting of histidine, serine and aspartate, and the tetrapeptide turn sequence comprises ‘Val-pro-Pro-Thr’; and wherein said peptide-based hydrogel is inherently a contrast agent; and
wherein said biocompatible CEST agent is configured to create contrast in an MR image detectable using a saturation transfer CEST method of MR imaging.
2. The agent of claim 1 wherein the peptide-based hydrogel further comprises at least one of lysine, arginine, ornithine, serine, threonine, histidine, tryptophan, and unnatural amino acids containing heterocyclic protons.
3. The agent of claim 1 wherein the peptide-based hydrogel produces a chemical shift of between approximately 1-15 ppm downfield from water.
4. The agent of claim 1 wherein the peptide-based hydrogel produces suitable exchange rates for generating CEST contrast in an MR machine.
5. The agent of claim 1 wherein the peptide-based hydrogel further comprises exchangeable protons.
6. The agent of claim 1 wherein the contents of the peptide based hydrogel are selected based on diffusion time, patient pH, biodegradability.
7. A method for magnetic resonance (MR) imaging of a subject comprising:
providing an agent as in claim 1
delivering the agent to the subject; and
using a chemical exchange saturation transfer agent (CEST) method of MR imaging to obtain an MR image of the subject.
8. The method of claim 7 wherein the peptide-based hydrogel comprises at least one of lysine, arginine, ornithine, serine, threonine, histidine, tryptophan, and unnatural amino acids containing heterocyclic protons.
9. The method of claim 7 wherein the peptide-based hydrogel produces a chemical shift of between approximately 1-15 ppm downfield from water.
10. The method of claim 7 wherein the peptide-based hydrogel produces suitable exchange rates for generating CEST contrast in an MR machine.
11. The method of claim 7 wherein the peptide-based hydrogel comprises exchangeable protons.
12. The method of claim 7 further comprising selecting the peptide based hydrogel based on diffusion time, patient pH, biodegradability.