Design of a Modular Protein-Based MRI Contrast Agent for Targeted Application |
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| Authors: | Daniel Grum Stefan Franke Oliver Kraff Dominik Heider Alexander Schramm Daniel Hoffmann Peter Bayer |
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| Institution: | 1. Research Group Structural and Medicinal Biochemistry, Centre for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.; 2. Research Group Bioinformatics, Centre for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.; 3. Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany.; 4. Department of Pediatric Hematology, University Children’s Hospital, Essen, Germany.; Stanford, United States of America, |
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| 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 Gd3+. 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. |
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