title: Rational design of protein-based MRI contrast agents.
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.
authors.affiliation: Department of Chemistry, Center for Drug Design and Advanced Biotechnology, Georgia State University, Atlanta, Georgia 30303, USA. chejjy@langate.gsu.edu
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Yang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yang
authors.forename: Lixia
authors.initials: L
authors.lastname: Wei
authors.forename: Omar
authors.initials: O
authors.lastname: Zurkiya
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Shunyi
authors.initials: S
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Zou
authors.forename: Yubin
authors.initials: Y
authors.lastname: Zhou
authors.forename: Anna L Wilkins
authors.initials: AL
authors.lastname: Maniccia
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Zhao
authors.forename: Russell
authors.initials: R
authors.lastname: Malchow
authors.forename: Shumin
authors.initials: S
authors.lastname: Zhao
authors.forename: Julian
authors.initials: J
authors.lastname: Johnson
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Hu
authors.forename: Eirik
authors.initials: E
authors.lastname: Krogstad
authors.forename: Zhi-Ren
authors.initials: ZR
authors.lastname: Liu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D018801:CD2 Antigens / Q000737:chemistry; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D005682:Gadolinium / Q000737:chemistry*; D019786:Gadolinium DTPA / Q000737:chemistry / Q000493:pharmacokinetics; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008667:Metalloproteins / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008958:Models, Molecular
chemical_list: D000906:Antibodies; D018801:CD2 Antigens; C038104:Ca1 antibody; D003287:Contrast Media; D008667:Metalloproteins; D005682:Gadolinium; D019786:Gadolinium DTPA