227457-56-9Relevant academic research and scientific papers
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
Aime, Silvio,Botta, Mauro,Frullano, Luca,Crich, Simonetta Geninatti,Giovenzana, Giovanni B.,Pagliarin, Roberto,Palmisano, Giovanni,Sisti, Massimo
, p. 1253 - 1260 (2007/10/03)
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. 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 GdIII complex containing this ligand shows a relaxivity of 8.25 mM-1 s-1 at 20 MHz and 25 °C. The hydrophobic p-bromo-benzyloxy moiety promotes the interaction of the chelate with human serum albumin (HSA) (Ka = 4×102 M-1) and with β-cyclodextrin (Ka = 8×102 M-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 32 mM-1 s-1 (20 MHz, 25 °C) when the concentrations are as follows: GdIII chelate 1 mM, poly-β-cyclodextrin 10 mM, HSA 0.58 mM. Under these conditions the GdIII chelate is mainly present as an inclusion compound with the poly-β-CD. This finding suggests a potential use for such a GdIII chelate/poly-β-CD system in MR angiographic applications.
