Contrast Agents for Magnetic Resonance Imaging: A Novel Route to Enhanced Relaxivities Based on the Interaction of a GdIII Chelate with Poly-β-cyclodextrins

This study proposes a novel route to improved contrast agents for magnetic resonance imaging (MRI) applications based on the formation of a non-covalent adduct between a paramagnetic complex and an exogeneous macromolecule. For this purpose a 12-membered pyridine-containing triacetate macrocyclic ligand with a p-bromobenzyloxy substituent on the pyridine moiety was synthesized. The GdIII complex containing this ligand shows a relaxivity of 8.25mM-1s-1 at 20 MHz and 25 C. The hydrophobic p-bromobenzyloxy moiety promotes the interaction of the chelate with human serum albumin (HSA) (Kaˆ4x102M-1) and with b-cyclodextrin (Ka8x102M-1). Upon replacing b-cyclodextrin with a poly-b-cyclodextrin substrate (MWˆ ca. 6000 Da) a further relaxation enhancement is detected as a consequence of the increased molecular size of the resulting inclusion compound. In a typical experiment in blood serum, the observed relaxivity is 32mM-1s-1 (20 MHz, 25 C) when the concentrations are as follows: GdIII chelate 1mM, poly-b-cyclodextrin 10mM, HSA 0.58mM. Under these conditions the GdIII chelate is mainly present as an inclusion compound with the poly-b-CD. This finding suggests a potential use for such a GdIII chelate/poly-b-CD system in MR angiographic applications.