title: Design of a modular protein-based MRI contrast agent for targeted application.
abstract: Magnetic resonance imaging (MRI) offers a non-radioactive alternative for the non-invasive detection of tumours. Low molecular weight MRI contrast agents currently in clinical use suffer either from a lack of specificity for tumour tissue or from low relaxivity and thus low contrast amplification. In this study, we present the newly designed two domain fusion protein Zarvin, which is able to bind to therapeutic IgG antibodies suitable for targeting, while facilitating contrast enhancement through high affinity binding sites for Gd(3+). We show that the Zarvin fold is stable under serum conditions, specifically targets a cancer cell-line when bound to the Cetuximab IgG, and allows for imaging with high relaxivity, a property that would be advantageous for the detection of small tumours and metastases at 1.5 or 3 T.
authors.affiliation: Research Group Structural and Medicinal Biochemistry, Centre for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grum
authors.forename: Stefan
authors.initials: S
authors.lastname: Franke
authors.forename: Oliver
authors.initials: O
authors.lastname: Kraff
authors.forename: Dominik
authors.initials: D
authors.lastname: Heider
authors.forename: Alexander
authors.initials: A
authors.lastname: Schramm
authors.forename: Daniel
authors.initials: D
authors.lastname: Hoffmann
authors.forename: Peter
authors.initials: P
authors.lastname: Bayer
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites; D045744:Cell Line, Tumor; D000068818:Cetuximab; D003287:Contrast Media / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D056004:Molecular Dynamics Simulation; D008970:Molecular Weight; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics; D012680:Sensitivity and Specificity
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003287:Contrast Media; D011993:Recombinant Fusion Proteins; C585571:zarvin protein; D005682:Gadolinium; D000068818:Cetuximab