Rational Design of Protein-Based MRI Contrast Agents
- 25 June 2008
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 130 (29), 9260-9267
- https://doi.org/10.1021/ja800736h
Abstract
We describe the rational design of a novel class of magnetic resonance imaging (MRI) contrast agents with engineered proteins (CAi.CD2, i = 1, 2,..., 9) chelated with gadolinium. The design of protein-based contrast agents involves creating high-coordination Gd3+ binding sites in a stable host protein using amino acid residues and water molecules as metal coordinating ligands. Designed proteins show strong selectivity for Gd3+ over physiological metal ions such as Ca2+, Zn2+, and Mg2+. These agents exhibit a 20-fold increase in longitudinal and transverse relaxation rate values over the conventional small-molecule contrast agents, e.g., Gd−DTPA (diethylene triamine pentaacetic acid), used clinically. Furthermore, they exhibit much stronger contrast enhancement and much longer blood retention time than Gd−DTPA in mice. With good biocompatibility and potential functionalities, these protein contrast agents may be used as molecular imaging probes to target disease markers, thereby extending applications of MRI.Keywords
This publication has 58 references indexed in Scilit:
- The inorganic side of chemical biologyNature Chemical Biology, 2006
- Translating in vivo diagnostics into clinical realityNature Biotechnology, 2006
- Paramagnetic lanthanide complexes as PARACEST agents for medical imagingChemical Society Reviews, 2006
- Strategies for increasing the sensitivity of gadolinium based MRI contrast agentsChemical Society Reviews, 2006
- Magnetic resonance microscopy: recent advances and applicationsCurrent Opinion in Biotechnology, 2005
- Targeting Cells with MR Imaging Probes Based on Paramagnetic Gd(III) ChelatesCurrent Pharmaceutical Biotechnology, 2004
- Relaxivity of MRI Contrast AgentsPublished by Springer Science and Business Media LLC ,2002
- In vivo visualization of gene expression using magnetic resonance imagingNature Biotechnology, 2000
- Number of inner‐sphere water molecules in Gd3+ and Eu3+ complexes of DTPA‐amide and ‐ester conjugatesMagnetic Resonance in Medicine, 1988
- Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and designChemical Reviews, 1987