Design of a Modular Protein-Based MRI Contrast Agent for Targeted Application

被引:14
作者
Grum, Daniel [1 ]
Franke, Stefan [2 ]
Kraff, Oliver [3 ]
Heider, Dominik [2 ]
Schramm, Alexander [4 ]
Hoffmann, Daniel [2 ]
Bayer, Peter [1 ]
机构
[1] Univ Duisburg Essen, Res Grp Struct & Med Biochem, Ctr Med Biotechnol, Essen, Germany
[2] Univ Duisburg Essen, Res Grp Bioinformat, Ctr Med Biotechnol, Essen, Germany
[3] Univ Duisburg Essen, Erwin L Hahn Inst Magnet Resonance Imaging, Essen, Germany
[4] Univ Childrens Hosp, Dept Pediat Hematol, Essen, Germany
关键词
EPIDERMAL-GROWTH-FACTOR; HIGHLY EFFICIENT; CARCINOMA-CELLS; BINDING; FLUORESCENCE; SIMULATION; GADOLINIUM; DOMAIN; FIELD; EGF;
D O I
10.1371/journal.pone.0065346
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:8
相关论文
共 35 条
[2]   Metal binding to cowpea chlorotic mottle virus using terbium(III) fluorescence [J].
Basu, G ;
Allen, M ;
Willits, D ;
Young, M ;
Douglas, T .
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, 2003, 8 (07) :721-725
[3]   PROTEIN DATA BANK - COMPUTER-BASED ARCHIVAL FILE FOR MACROMOLECULAR STRUCTURES [J].
BERNSTEIN, FC ;
KOETZLE, TF ;
WILLIAMS, GJB ;
MEYER, EF ;
BRICE, MD ;
RODGERS, JR ;
KENNARD, O ;
SHIMANOUCHI, T ;
TASUMI, M .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1977, 80 (02) :319-324
[4]  
Bernstein MA, 2004, HDB MRI PULSE SEQUEN, P608
[5]  
Brücher E, 2002, TOP CURR CHEM, V221, P103
[6]   Strategies for increasing the sensitivity of gadolinium based MRI contrast agents [J].
Caravan, Peter .
CHEMICAL SOCIETY REVIEWS, 2006, 35 (06) :512-523
[7]   Influence of molecular parameters and increasing magnetic field strength on relaxivity of gadolinium- and manganese-based T1 contrast agents [J].
Caravan, Peter ;
Farrar, Christian T. ;
Frullano, Luca ;
Uppal, Ritika .
CONTRAST MEDIA & MOLECULAR IMAGING, 2009, 4 (02) :89-100
[8]  
CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099
[9]  
Daura X, 1998, J COMPUT CHEM, V19, P535, DOI 10.1002/(SICI)1096-987X(19980415)19:5<535::AID-JCC6>3.0.CO
[10]  
2-N