Synthesis and Physicochemical Characterisation of Gd‐DTPA Derivatives as Contrast Agents for MRI

Abstract

Abstract Paramagnetic magnetic resonance imaging (MRI) contrast agents are the compounds most used in clinical studies. Among these, the derivatives of Gd‐DTPA (gadoliniumdiethylenetriaminepentaacetic acid, Magnevist ® , Bayer HealthCare) have been extensively studied. The first part of this work consists of a comparison of various derivatives of Gd‐DTPA [mono‐, bis‐ or pentaamides; C ‐functionalised (C 2 , C 4 , C 5 , N 6 ) or diester derivatives] according to their synthesis and to the most important parameters that regulate their efficacy. The synthesis of bis(amide)s consists of only one step and is thus easier than the synthesis of the C 4 derivatives, which needs several steps and requires a tedious purification. These last compounds are, however, more stable against transmetallation with another ion such as zinc [more than 50 % of the gadolinium complex remains after 4300 min while this percentage falls under 40 % for most of the bis(amide) compounds] and generally have higher relaxivities. Moreover, the residence time of the water molecule in the first coordination sphere of the gadolinium complex ( τ M ) is shorter for the C 4 derivatives and does not limit the relaxivity. In the second part of this work, an overview of different kinds of recently developed paramagnetic contrast agents is presented: new systems to improve the relaxivity, like fullerenol compounds, apoferritin or zeolite complexes, lipophilic complexes (in structures like micelles or liposomes), macromolecular products as well as small complexes interacting with human serum albumin (HSA).