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

Mani Salarian, Ravi Chakra Turaga, Shenghui Xue, Maysam Nezafati, Khan Hekmatyar, Jingjuan Qiao, Yinwei Zhang, Shanshan Tan, Oluwatosin Y. Ibhagui, Yan Hai, Jibiao Li, Rao Mukkavilli, Malvika Sharma, Pardeep Mittal, Xiaoyi Min, Shella Keilholz, Liqing Yu, Gengshen Qin, Alton Brad Farris, Zhi-Ren Liu and Jenny J. Yang ()
Additional contact information
Mani Salarian: Georgia State University
Ravi Chakra Turaga: Georgia State University
Shenghui Xue: Georgia State University
Maysam Nezafati: Emory University and Georgia Institute of Technology
Khan Hekmatyar: University of Georgia
Jingjuan Qiao: Georgia State University
Yinwei Zhang: Georgia State University
Shanshan Tan: Georgia State University
Oluwatosin Y. Ibhagui: Georgia State University
Yan Hai: Georgia State University
Jibiao Li: Georgia State University
Rao Mukkavilli: Georgia State University
Malvika Sharma: Georgia State University
Pardeep Mittal: Augusta University
Xiaoyi Min: Georgia State University
Shella Keilholz: Emory University and Georgia Institute of Technology
Liqing Yu: Georgia State University
Gengshen Qin: Georgia State University
Alton Brad Farris: Emory University School of Medicine
Zhi-Ren Liu: Georgia State University
Jenny J. Yang: Georgia State University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11984-2

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