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Preparation, Purification, and Characterization of Lanthanide Complexes for Use as Contrast Agents for Magnetic Resonance Imaging
Published on: July 21, 2011
Tailoring encodable lanthanide-binding tags as MRI contrast agents.
Kelly D Daughtry1, Langdon J Martin, Ashish Sarraju
1Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02218, USA.
Chembiochem : a European Journal of Chemical Biology
|November 15, 2012
Summary
Researchers engineered lanthanide-binding tags (LBTs) into novel MRI contrast agents. These modified LBTs enhance water coordination for improved magnetic resonance imaging (MRI) contrast, paving the way for targeted imaging agents.
Area of Science:
- Biochemistry
- Biophysics
- Medical Imaging
Background:
- Lanthanide-binding tags (LBTs) are peptide tags with high affinity for lanthanide ions.
- LBTs have been used in X-ray crystallography and NMR for structural determination.
- Native LBTs bind Gd(3+) but their coordination state is not optimal for MRI contrast agents due to limited water access.
Purpose of the Study:
- To re-engineer LBTs for enhanced MRI contrast agent properties.
- To create peptide-based MRI agents with improved water coordination to Gd(3+).
- To develop targeted MRI contrast agents by fusing engineered LBTs to specific proteins.
Main Methods:
- Structural modification of LBTs to create the m-sLBT peptide for direct water coordination to Gd(3+).
- In vitro assessment of binding affinity and proton relaxivity of engineered LBTs.
- Construction and structural analysis (X-ray crystallography) of fusion proteins (dLBT-ubiquitin and q-dLBT-ubiquitin) to understand relaxivity differences.
Main Results:
- Engineered LBTs (m-sLBT) demonstrated potential for high MRI contrast through direct water coordination.
- Fusion of a double LBT (dLBT) to ubiquitin initially reduced relaxivity.
- A modified construct (q-dLBT-ubiquitin) based on m-sLBT sequence restored and potentially enhanced relaxivity.
- Structural analysis revealed backbone conformational dynamics in the MRI variant may facilitate enhanced water exchange.
Conclusions:
- Engineered LBTs provide a basis for novel peptide-based MRI contrast agents.
- The q-dLBT-ubiquitin construct shows promise for targeted MRI applications.
- This work represents a significant step towards developing specificity-targeted MRI agents.
