title: Optimized relaxivity and stability of [Gd(H(2,2)-1,2-HOPO)(H2O)]- for use as an MRI contrast agent.
abstract: Relaxometry and solution thermodynamic measurements show that Gd(H(2,2)-1,2-HOPO) is a good candidate as a contrast agent for magnetic resonance imaging (MRI-CA). Acidic, octadentate H(2,2)-1,2-HOPO forms a very stable Gd(III) complex [pGd=21.2(2)]. The coordination sphere at the Gd(III) center is completed by one water molecule that is not replaced by common physiological anions. In addition, this ligand is highly selective for Gd(III) binding in the presence of Zn(II) or Ca(II). The symmetric charge distribution of the 1,2-HOPO chelates is associated with favorably long electronic relaxation time T1,2e comparable to those of GdDOTA. This, in addition to the fast water exchange rate typical of HOPO chelates, improves the relaxivity to r1p=8.2 mM-1 s-1 (0.47 T). This remarkably high value is unprecedented for small-molecule, q=1 MRI-CA.
authors.affiliation: Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Jocher
authors.forename: Mauro
authors.initials: M
authors.lastname: Botta
authors.forename: Stefano
authors.initials: S
authors.lastname: Avedano
authors.forename: Evan G
authors.initials: EG
authors.lastname: Moore
authors.forename: Jide
authors.initials: J
authors.lastname: Xu
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Raymond
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D004355:Drug Stability; D005682:Gadolinium; D008024:Ligands; D008279:Magnetic Resonance Imaging / Q000379:methods*; D013816:Thermodynamics
chemical_list: D003287:Contrast Media; D008024:Ligands; D005682:Gadolinium