Improving T 1 and T 2 magnetic resonance imaging contrast agents through the conjugation of an esteramide dendrimer to high‐water‐coordination Gd(III) hydroxypyridinone complexes

Commercial gadolinium magnetic resonance imaging (MRI) contrast agents are limited by low relaxivity ( r 1 ) and coordination to only a single water molecule ( q  = 1). Consequently, gram quantities of these agents must be injected to obtain sufficient diagnostic contrast. In this study, MRI contrast agents for T 1 and T 2 relaxivity were synthesized using hydroxypyridinone and terephthalamide chelators with mesityl and 1,4,7‐triazacyclononane capping moieties. When covalently conjugated to a highly biocompatible esteramide dendrimer, T 2 relaxation rates up to 52 m m −1  s −1 and T 1 relaxation rates up to 31 m m −1  s −1 per gadolinium were observed under clinically relevant conditions. These values are believed to be brought about by using a dendritic macromolecule to decrease the molecular tumbling time of the small molecule complexes. These agents also show high aqueous solubility and low toxicity in vitro . In this study we report six new compounds: three discrete complexes and three dendrimer conjugates. Copyright © 2012 John Wiley & Sons, Ltd.