Design of a modular protein-based MRI contrast agent for targeted application

PLoS One. 2013 Jun 6;8(6):e65346. doi: 10.1371/journal.pone.0065346. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / chemistry*
  • Antibodies, Monoclonal, Humanized / immunology
  • Binding Sites
  • Cell Line, Tumor
  • Cetuximab
  • Contrast Media / chemistry*
  • Crystallography, X-Ray
  • Gadolinium / chemistry*
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Molecular Dynamics Simulation
  • Molecular Weight
  • Protein Binding
  • Protein Folding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry*
  • Recombinant Fusion Proteins / genetics
  • Sensitivity and Specificity

Substances

  • Antibodies, Monoclonal, Humanized
  • Contrast Media
  • Recombinant Fusion Proteins
  • zarvin protein
  • Gadolinium
  • Cetuximab

Associated data

  • PDB/1Q2N
  • PDB/1S3P

Grants and funding

This work was supported by the “Bundesministerium für Bildung und Forschung” (BMBF; 01EZ093 1–4). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.