Abstract: The present disclosure relates to magnetic resonance imaging (MRI) using biochemically responsive imaging probes that can be used in, for example, non-invasive pH mapping in cancer and/or diseases characterized by aberrant metabolism using contrast enhanced MRI.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Manganese coordination complexes with utility as magnetic resonance probes and as biological reductant sensors are disclosed. In one embodiment, ligands can stabilize both the Mn2+ and Mn3+ oxidation states. In the presence of a reductant such as glutathione, low relaxivity MnIII-HBET is rapidly converted to high relaxivity MnII-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.

Abstract: Manganese coordination complexes with utility as magnetic resonance probes and as biological reductant sensors are disclosed. In one embodiment, ligands can stabilize both the Mn2+ and Mn3+ oxidation states. In the presence of a reductant such as glutathione, low relaxivity MnIII-HBET is rapidly converted to high relaxivity MnII-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.

Abstract: A method for increasing the relaxivity of a contrast agent having a metal ion complexed to a chelator is disclosed. The metal ion complex is tethered to the remainder of the molecule by at least two points of attachment such that local motion is limited and higher relaxivity can be achieved. In one non-limiting example version of the invention, the alanine analogue of Gd(DOTA), Gd(DOTAla) wherein Gd is gadolinium and DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid was integrated into polypeptide structures. This resulted in very rigid attachment of the metal ion complex to the peptide backbone. Rigid molecular structures provide fewer degrees of rotational freedom, resulting in greater control over the rotational dynamics and resultant relaxivity. In the case of Gd(DOTAla), the metal complex is tethered to the peptide via the amino acid side chain to the DOTA moiety and via a dative bond from an amide oxygen to the Gd(III) ion.