A New Gadolinium-Based MRI Zinc Sensor

• Published in: Journal of the American Chemical Society Vol. 131; no. 32; pp. 11387 - 11391
• Main Authors: Esqueda, Ana C., López, Jorge A., Andreu-de-Riquer, Gabriel, Alvarado-Monzón, José C., Ratnakar, James, Lubag, Angelo J. M., Sherry, A. Dean, De León-Rodríguez, Luis M.
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 19.08.2009; Amer Chemical Soc
• Subjects: Binding Sites; Chemistry; Chemistry, Multidisciplinary; Contrast Media - chemistry; Contrast Media - metabolism; Gadolinium - chemistry; Gadolinium - metabolism; Humans; Magnetic Resonance Imaging - methods; Models, Molecular; Physical Sciences; Protein Binding; Science & Technology; Sensitivity and Specificity; Serum Albumin - metabolism; Zinc - analysis; Zinc - metabolism; AGENT; MAGNETIC-RESONANCE; IONS; COMPLEX; HUMAN SERUM; BINDING
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja901875v

The properties of a novel Gd3+-based MRI zinc sensor are reported. Unlike previously reported Gd3+-based MRI contrast agents, this agent (GdL) differs in that the agent alone binds only weakly with human serum albumin (HSA), while the 1:2 GdL:Zn2+ ternary complex binds strongly to HSA resulting in a substantial, 3-fold increase in water proton relaxivity. The GdL complex is shown to have a relatively strong binding affinity for Zn2+ (K D = 33.6 nM), similar to the affinity of the Zn2+ ion with HSA alone. The agent detects as little as 30 μM Zn2+ in the presence of HSA by MRI in vitro, a value slightly more than the total Zn2+ concentration in blood (∼20 μM). This combination of binding affinity constants and the high relaxivity of the agent when bound to HSA suggests that this new agent may be useful for detection of free Zn2+ ions in vivo without disrupting other important biological processes involving Zn2+.