title: Strategies for the covalent conjugation of a bifunctional chelating agent to albumin: synthesis and characterization of potential MRI contrast agents.
abstract: With the purpose to develop macromolecular magnetic resonance imaging contrast agents, we herein report three different synthetic approaches to the covalent attachment of bifunctional chelating agents to human serum albumin followed by coordination to contrast enhancing gadolinium(III). Applied methods cover active ester-mediated conjugation, linkage through glutaryl spacer, as well as the connection by the employment of glutaraldehyde. The content of gadolinium(III) was evaluated by inductively-coupled-plasma mass-spectrometry (ICP-MS) measurements and indicated reproducible amounts of conjugated contrast enhancing material. Small angle X-ray scattering (SAXS) experiments provided the size and altered shape of the gadolinium loaded proteins in comparison to unmodified albumin. Finally, the magnetic resonance properties of the protein conjugates were evaluated. The results indicated suitability of the gadolinium(III) loaded protein conjugates for use as macromolecular contrast agents in magnetic resonance imaging (MRI).
authors.affiliation: University of Vienna, Institute of Inorganic Chemistry, Währinger Strasse 42, A-1090 Vienna, Austria.
authors.forename: Amitava
authors.initials: A
authors.lastname: Kundu
authors.forename: Herwig
authors.initials: H
authors.lastname: Peterlik
authors.forename: Martin
authors.initials: M
authors.lastname: Krssak
authors.forename: Anna K
authors.initials: AK
authors.lastname: Bytzek
authors.forename: Irena
authors.initials: I
authors.lastname: Pashkunova-Martic
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Arion
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Helbich
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
mesh_terms: D002614:Chelating Agents / Q000737:chemistry*; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry; D005682:Gadolinium; D006801:Humans; D008279:Magnetic Resonance Imaging; D008968:Molecular Conformation; D053838:Scattering, Small Angle; D012709:Serum Albumin / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D056831:Coordination Complexes; D012709:Serum Albumin; D005682:Gadolinium