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Abstract #1890

Thiol Complexes of Gadolinium for Imaging Therapy-Induced Oxidative Stress in Pre-Clinical Tumors

Bhumasamudram Jagadish1, Gerald P. Guntle2, Vijay Gokhale3, Amanda F. Baker2, Eugene A. Mash1, Natarajan Raghunand4

1Chemistry, The University of Arizona, Tucson, AZ, United States; 2Cancer Center, The University of Arizona, Tucson, AZ, United States; 3Pharmacology & Toxicology, The University of Arizona, Tucson, AZ, United States; 4Radiology, The University of Arizona, Tucson, AZ, United States


DO3A- and DOTA-based thiol complexes of gadolinium have been synthesized and characterized. The molecules are designed to covalently bind the conserved cysteine-34 site in circulating plasma albumin. Redox-sensitivity is conferred by differential relaxivities of the albumin-bound (in oxidizing microenvironments) and unbound (in reducing microenvironments) forms of the complexes. Oxidative stress was induced in tumor-bearing mice by 2-deoxyglucose challenge. The change in tumor T1 following administration of a candidate thiol complex of Gd was significantly lower in treated mice relative to control mice. This is consistent with a 2DG-induced ARE-driven reduction of the tumor microenvironment, and supporting evidence will be presented.

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