Conjugation to biocompatible dendrimers increases lanthanide T₂ relaxivity of hydroxypyridinone complexes for magnetic resonance imaging

Magnetic resonance imaging (MRI) contrast agents represent a worldwide billion-dollar market annually. While T₁ relaxivity enhancement contrast agents receive greater attention and a significantly larger market share, the commercial potential for T₂ 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 T₂ MRI probes may enable new diagnostic prospects for MRI. Paramagnetic lanthanides have the potential to decrease T₁ and T ₂ proton relaxation times, but are not commercially used in MRI diagnostics as T₂ 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 T₂ MRI probes. These conjugates have relaxivities of up to 374 mM^-1 s^-1 per dendrimer, high bioavailability, and low in vitro toxicity. The development of high relaxivity andbiofunctional MRI probes is essential to increasing clinical diagnostic ability. T₂ MRI probes using lanthanides have the potential to increase relaxivity, biocompatibility, and offer the prospective to increase imaging modality functions.