Contrast agents for magnetic resonance imaging: A novel route to enhanced relaxivities based on the interaction of a Gd(III) 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 triacerate macrocyclic ligand with a p-bromobenzyloxy substituent on the pyridine moiety was synthesized. The Gd(III) complex containing this ligand shows a relaxivity of 8.25mM^-1S^-1 at 20MHz and 25°C. The hydrophobic p-bromo- benzyloxy moiety promotes the interaction of the chelate with human serum albumin (HSA) (K(a) x 10²M^-1) and with β-cyclodextrin (K(a) = 8 x 10²M^{- 1}). Upon replacing β-cyclodextrin with a poly-β-cyclodextrin substrate (MW = 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: Gd(III) chelate I mM, poly-β-cyclodextrin 10mM, HSA 0.58mm. Under these conditions the Gd(III) chelate is mainly present as an inclusion compound with the poly-β-CD. This finding suggests a potential use for such a Gd(III) chelate/poly-β-CD system in MR angiographic applications.