1. Rational design of protein-based MRI contrast agents.
- Author
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Yang JJ, Yang J, Wei L, Zurkiya O, Yang W, Li S, Zou J, Zhou Y, Maniccia AL, Mao H, Zhao F, Malchow R, Zhao S, Johnson J, Hu X, Krogstad E, and Liu ZR
- Subjects
- Animals, Antibodies chemistry, CD2 Antigens chemistry, Contrast Media chemistry, Contrast Media pharmacokinetics, Gadolinium DTPA chemistry, Gadolinium DTPA pharmacokinetics, Kinetics, Metalloproteins chemistry, Metalloproteins pharmacokinetics, Mice, Models, Molecular, Contrast Media chemical synthesis, Gadolinium chemistry, Magnetic Resonance Imaging methods, Metalloproteins chemical synthesis
- 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 Gd(3+) binding sites in a stable host protein using amino acid residues and water molecules as metal coordinating ligands. Designed proteins show strong selectivity for Gd(3+) over physiological metal ions such as Ca(2+), Zn(2+), and Mg(2+). 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.
- Published
- 2008
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