Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents.
This paper compares the physicochemical properties of six low molecular weight clinical complexes of gadolinium studied under identical experimental conditions. Magnevist, Dotarem, Omniscan, ProHance, MultiHance and Gadovist were investigated by oxygen-17 relaxometry at different temperatures and by proton relaxometry at various magnetic fields, temperatures and media [pure water, zinc(II)-containing aqueous solutions and HSA-containing solutions]. Osmolality, viscosity and stability versus transmetallation by zinc(II) ions were added for a more comprehensive description. The relaxivities of the clinical formulations as measured in water are similar in the imaging magnetic field region, with a slightly better performance for MultiHance. This can be explained by a shorter distance between the hydrogen nuclei of the water molecule bound to the Gd(3+) ion and this paramagnetic centre. In contrast to the open-chain complexes, all macrocyclic systems (Dotarem, ProHance and Gadovist) are insensitive to transmetallation by zinc ions. The stability of the open-chain complexes with respect to transmetallation depends on the chemical structure of the ligand, with a better stability for MultiHance. The presence of human serum albumin has no significant effect on the proton relaxivity of Magnevist, Dotarem, Omniscan, ProHance and Gadovist but markedly increases the relaxivity of MultiHance because of a non-covalent interaction with the protein. As a result, the relaxivity of MultiHance in HSA-containing media of fixed concentration decreases with increasing concentration of the contrast agent.
Laurent
Sophie
S
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, 24 Avenue du Champ de Mars, B-7000 Mons, Belgium.
Elst
Luce Vander
LV
Muller
Robert N
RN
D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics*; D004355:Drug Stability; D005682:Gadolinium / Q000737:chemistry* / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA / Q000737:chemistry / Q000493:pharmacokinetics; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008536:Meglumine / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D008954:Models, Biological; D008970:Molecular Weight; D019906:Nuclear Magnetic Resonance, Biomolecular; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D010103:Oxygen Isotopes / Q000737:chemistry; D011485:Protein Binding; D011522:Protons; D012709:Serum Albumin / Q000378:metabolism; D013696:Temperature; D014867:Water / Q000737:chemistry; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D010103:Oxygen Isotopes; D011522:Protons; D012709:Serum Albumin; C062402:gadoteridol; D014867:Water; C064572:gadobenic acid; C090600:gadobutrol; D008536:Meglumine; C064925:gadodiamide; D005682:Gadolinium; D015032:Zinc; D019786:Gadolinium DTPA; C072417:gadoterate meglumine