Conjugation to Biocompatible Dendrimers Increases Lanthanide <i>T</i>₂ Relaxivity of Hydroxypyridinone Complexes for Magnetic Resonance Imaging

Abstract Magnetic resonance imaging (MRI) contrast agents represent a worldwide billion‐dollar market annually. While T 1 relaxivity enhancement contrast agents receive greater attention and a significantly larger market share, the commercial potential for T 2 relaxivity enhancing contrast agents remains a viable diagnostic option because of their increased relaxivity at high field strengths. Improvement of the contrast and biocompatibility of T 2 MRI probes may enable new diagnostic prospects for MRI. Paramagnetic lanthanides have the potential to decrease T 1 and T 2 proton relaxation times, but are not commercially used in MRI diagnostics as T 2 agents. In this article, oxygen donor chelates (hydroxypyridinone, HOPO, and terephthalamide, TAM) of various lanthanides are demonstrated as biocompatible macromolecular dendrimer conjugates for the development of T 2 MRI probes. These conjugates have relaxivities of up to 374 m M –1 s –1 per dendrimer, high bioavailability, and low in vitro toxicity.