A new gadolinium-based MRI zinc sensor.
The properties of a novel Gd(3+)-based MRI zinc sensor are reported. Unlike previously reported Gd(3+)-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:Zn(2+) 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 Zn(2+) (K(D) = 33.6 nM), similar to the affinity of the Zn(2+) ion with HSA alone. The agent detects as little as 30 microM Zn(2+) in the presence of HSA by MRI in vitro, a value slightly more than the total Zn(2+) concentration in blood (approximately 20 microM). 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 Zn(2+) ions in vivo without disrupting other important biological processes involving Zn(2+).
Esqueda
Ana C
AC
Departamento de Química, Universidad de Guanajuato, Cerro de la Venada s/n, Guanajuato, Gto., C.P. 36040, México.
López
Jorge A
JA
Andreu-de-Riquer
Gabriel
G
Alvarado-Monzón
José C
JC
Ratnakar
James
J
Lubag
Angelo J M
AJ
Sherry
A Dean
AD
De León-Rodríguez
Luis M
LM
D001665:Binding Sites; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008958:Models, Molecular; D011485:Protein Binding; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000378:metabolism; D015032:Zinc / Q000032:analysis* / Q000378:metabolism
D003287:Contrast Media; D012709:Serum Albumin; D005682:Gadolinium; D015032:Zinc