Abstract

Early diagnosis and noninvasive detection of liver fibrosis and its heterogeneity remain as major unmet medical needs for stopping further disease progression toward severe clinical consequences. Here we report a collagen type I targeting protein-based contrast agent (ProCA32.collagen1) with strong collagen I affinity. ProCA32.collagen1 possesses high relaxivities per particle (r1 and r2) at both 1.4 and 7.0 T, which enables the robust detection of early-stage (Ishak stage 3 of 6) liver fibrosis and nonalcoholic steatohepatitis (Ishak stage 1 of 6 or 1 A Mild) in animal models via dual contrast modes. ProCA32.collagen1 also demonstrates vasculature changes associated with intrahepatic angiogenesis and portal hypertension during late-stage fibrosis, and heterogeneity via serial molecular imaging. ProCA32.collagen1 mitigates metal toxicity due to lower dosage and strong resistance to transmetallation and unprecedented metal selectivity for Gd3+ over physiological metal ions with strong translational potential in facilitating effective treatment to halt further chronic liver disease progression.

Details

Title
Early detection and staging of chronic liver diseases with a protein MRI contrast agent
Author
Salarian, Mani 1 ; Ravi Chakra Turaga 2   VIAFID ORCID Logo  ; Xue, Shenghui 1   VIAFID ORCID Logo  ; Nezafati, Maysam 3 ; Khan Hekmatyar 4 ; Qiao, Jingjuan 1 ; Zhang, Yinwei 2 ; Tan, Shanshan 1 ; Ibhagui, Oluwatosin Y 1 ; Yan, Hai 5 ; Li, Jibiao 6 ; Rao Mukkavilli 7 ; Sharma, Malvika 2 ; Mittal, Pardeep 8 ; Min, Xiaoyi 5 ; Keilholz, Shella 3 ; Yu, Liqing 6 ; Gengshen Qin 5 ; Alton Brad Farris 9   VIAFID ORCID Logo  ; Liu, Zhi-Ren 10 ; Yang, Jenny J 11 

1  Department of Chemistry, Georgia State University, Atlanta, GA, USA 
2  Department of Biology, Georgia State University, Atlanta, GA, USA 
3  Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, USA 
4  Bioimaging Research Center, University of Georgia, Athens, GA, USA 
5  Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, USA 
6  Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA, USA 
7  Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA 
8  Medical College of Georgia, Augusta University, Augusta, Georgia 
9  Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA 
10  Department of Biology, Georgia State University, Atlanta, GA, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA 
11  Department of Chemistry, Georgia State University, Atlanta, GA, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA 
Pages
1-14
Publication year
2019
Publication date
Oct 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-11984-2
ProQuest document ID
2310419487
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.