Rational design of protein-based MRI contrast agents.
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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.
author list (cited authors)
Yang, J. J., Yang, J., Wei, L., Zurkiya, O., Yang, W., Li, S., ... Liu, Z.
complete list of authors
Yang, Jenny J||Yang, Jianhua||Wei, Lixia||Zurkiya, Omar||Yang, Wei||Li, Shunyi||Zou, Jin||Zhou, Yubin||Maniccia, Anna L Wilkins||Mao, Hui||Zhao, Fuqiang||Malchow, Russell||Zhao, Shumin||Johnson, Julian||Hu, Xiaoping||Krogstad, Eirik||Liu, Zhi-Ren