Strategies for the covalent conjugation of a bifunctional chelating agent to albumin: Synthesis and characterization of potential MRI contrast agents

Author(s)

Amitava Kundu, Herwig Peterlik, Martin Krssak, Anna Bytzek, Irena Pashkunova-Martic, Vladimir Arion, Thomas H Helbich, Bernhard Keppler

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).

Organisation(s)

Department of Inorganic Chemistry, Dynamics of Condensed Systems

External organisation(s)

Medizinische Universität Wien

Journal

Journal of Inorganic Biochemistry

Volume

105

Pages

250-255

No. of pages

6

ISSN

0162-0134

DOI

https://doi.org/10.1016/j.jinorgbio.2010.10.015

Publication date

2011

Peer reviewed

Yes

Austrian Fields of Science 2012

104003 Inorganic chemistry, 103018 Materials physics, 301304 Medical biology

Portal url

https://ucrisportal.univie.ac.at/en/publications/a917e756-fdf7-41a0-b47e-7e0bf68407f4