Rational design of protein-based MRI contrast agents.
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.
Yang
Jenny J
JJ
Department of Chemistry, Center for Drug Design and Advanced Biotechnology, Georgia State University, Atlanta, Georgia 30303, USA. chejjy@langate.gsu.edu
Yang
Jianhua
J
Wei
Lixia
L
Zurkiya
Omar
O
Yang
Wei
W
Li
Shunyi
S
Zou
Jin
J
Zhou
Yubin
Y
Maniccia
Anna L Wilkins
AL
Mao
Hui
H
Zhao
Fuqiang
F
Malchow
Russell
R
Zhao
Shumin
S
Johnson
Julian
J
Hu
Xiaoping
X
Krogstad
Eirik
E
Liu
Zhi-Ren
ZR
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
D000906:Antibodies; D018801:CD2 Antigens; C038104:Ca1 antibody; D003287:Contrast Media; D008667:Metalloproteins; D005682:Gadolinium; D019786:Gadolinium DTPA