Contrast agents for magnetic resonance imaging: A novel route to enhanced relaxivities based on the interaction of a Gd-III chelate with poly-beta-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-bromo-benzyloxy substituent on the pyridine moiety was synthesized. The Gd-III complex containing this ligand shows a relaxivity of 8.25 mM(-1)s(-1) at 20 MHz and 25 degrees C The hydrophobic p-bromo-benzyloxy moiety promotes the interaction of the chelate with human serum albumin (HSA) (K-a = 4 x 10(2) M-1) and with beta-cyclodextrin (K-a = 8 x 10(2) M-1). Upon replacing beta-cyclodextrin with a poly-beta-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 32 mM(-1) s(-1) (20 MHz, 25 degrees C) when the concentrations are as follows: Gd-III chelate 1 mM, poly-beta-cyclodextrin 10 mM, HSA 0.58 mM. Under these conditions the Gd-III chelate is mainly present as an inclusion compound with the poly-beta-CD. This finding suggests a potential use for such a Gd-III chelate/poly-beta-CD system in MR angiographic applications.