title: In vitro neurotoxicity of magnetic resonance imaging (MRI) contrast agents: influence of the molecular structure and paramagnetic ion.
abstract: Interest in contrast agent's (CA) neurotoxicity has greatly increased due to the growing need of new compounds dedicated to brain imaging. Magnetic resonance imaging (MRI) CA have been evaluated by means of different toxicological assays with cultured rat primary neurons (evaluation of neurite specific parameters via immunostaining of the cells and LDH leakage). To determine the potential neurotoxicity of a precise paramagnetic ion in a defined structure (architecture and molecular weight), novel hydrosoluble dendritic Manganese (II) and Gadolinium (III) complexes derived from diethylenetriamine pentaacetic acid (DTPA) have been studied and compared to a linear homologue (same molecular weight) and commercially available low molecular weight MRI CA like Mn-DPDP (Teslascan, GE Healthcare) and Gd-DTPA (Magnevist, Schering). The range of CA concentrations studied was 0.1-10mM, suitable for MRI examinations. This set of experiments allows a toxicity ranking of these reagents as a function of molecular structure and nature of the paramagnetic ion. We could determine that the architecture (linear vs. dendritic) does not play an important role in the in vitro neurotoxicity, whereas the structure of the chelating cage is of greater importance.
authors.affiliation: Institut de Physique et Chimie des Matériaux de Strasbourg - Groupe des Matériaux Organiques, 23 Rue du Loess BP 43, 67034 Strasbourg Cedex 2, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Bertin
authors.forename: Anne-Isabelle
authors.initials: AI
authors.lastname: Michou-Gallani
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Gallani
authors.forename: Delphine
authors.initials: D
authors.lastname: Felder-Flesch
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003287:Contrast Media / Q000737:chemistry / Q000633:toxicity*; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D019786:Gadolinium DTPA / Q000737:chemistry / Q000633:toxicity*; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D051381:Rats
chemical_list: D003287:Contrast Media; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; D045022:Lactate Dehydrogenases; D019786:Gadolinium DTPA; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid