Commercial MRI contrast agents (CA) struggle with low relaxivity, requiring gram quantity injections to obtain a signal. CA can be improved through increasing molecular weight, increasing the number of inner sphere water molecules coordinated to the metal center (q), and increasing water exchange rate. These parameters must be improved without sacrificing solubility, bioavailibility, rapid renal clearance, and kinetic stability. Hexadentate Gd-HOPO complexes maintain high stability through the six oxygen donor chelating atoms, while allowing a relaxivity increase of 2-3 fold with a q = 2-3. Molecular weight is increased through a short, rigid linker to a macromolecule, such as a gold nanoparticle. A short, rigid linker allows the Gd(III) center local motion to be slowed as much as possible by the macromolecule global motion. With these parameters improved, a high relaxivity contrast agent has been synthesized while maintaining biological parameters.

Synthesis of macromolecular gadolinium hydroxypyridinone (HOPO) complexes as magnetic resonance imaging (MRI) contrast agents

243rd National Meeting (2012)

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