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Nat Commun. 2019 Oct 29;10(1):4777. doi: 10.1038/s41467-019-11984-2.

Early detection and staging of chronic liver diseases with a protein MRI contrast agent.

Author information

1
Department of Chemistry, Georgia State University, Atlanta, GA, 30303, USA.
2
Department of Biology, Georgia State University, Atlanta, GA, 30303, USA.
3
Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, 30322, USA.
4
Bioimaging Research Center, University of Georgia, Athens, GA, 30602, USA.
5
Department of Mathematics and Statistics, Georgia State University, Atlanta, GA, 30303, USA.
6
Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA, 30303, USA.
7
Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA.
8
Medical College of Georgia, Augusta University, Augusta, 30912, Georgia.
9
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, 30307, USA.
10
Department of Chemistry, Georgia State University, Atlanta, GA, 30303, USA. jenny@gsu.edu.
11
Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA. jenny@gsu.edu.

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.

Comment in

PMID:
31664017
PMCID:
PMC6820552
DOI:
10.1038/s41467-019-11984-2
[Indexed for MEDLINE]
Free PMC Article

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