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Abstract #1858

Redox-Sensitive Contrast Agents for MRI Based on Reversible Binding of Thiols to Serum Albumin

Raghunand N, Jagadish B, Trouard T, Gillies R, Mash E
University of Arizona

DOTA-based thiol complexes of gadolinium were synthesized. It was hypothesized that these complexes would form reversible covalent linkages with human serum albumin (HSA) which contains a reactive thiol at cysteine-34. The binding constants of both complexes to HSA, and their longitudinal water-proton relaxivities, were measured in the absence and presence of homocysteine, a competing thiol. Their in vivo pharmacokinetics were followed by DCE-MRI, and could be altered by a chase of homocysteine but not saline. Such spontaneous, redox-sensitive and reversible binding of gadolinium complexes to circulating albumin can be exploited for imaging tissue redox and the blood-pool by MRI.