The General Hospital Corporation

Eric M Gale

Peter Caravan

Galen S Loving

Jiang Zhu

Shereya Mukherjee

Provided herein are examples of metal chelating ligands that have high affinity for manganese. The resultant metal complexes can be used as MRI contrast agents, and can be functionalized with moieties that bind to or cause relaxivity change in the presence of biochemical targets.

Manganese-based chelate conjugates for molecular MR imaging

Manganese coordination complexes with utility as magnetic resonance probes and as biological reductant sensors are disclosed. In one embodiment, ligands can stabilize both the Mnand Mnoxidation states. In the presence of a reductant such as glutathione, low relaxivity Mn-HBET is rapidly converted to high relaxivity Mn-HBET with a 3-fold increase in relaxivity, and concomitant increase in magnetic resonance signal. In another embodiment, ligands were designed to chelate Mn(ll) in a thermodynamically stable and kinetically inert fashion while allowing for direct interaction of Mn(ll) with water. In yet another embodiment, high molecular weight multimers containing six Mn(ll) chelators were prepared. The high molecular weight results in slower tumbling of the molecules in solution and can strongly enhance the Mn(ll) relaxivity.

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Charlestown, MA, United States of America

Eric M Gale