Early detection and staging of chronic liver diseases with a protein MRI contrast agent
Early detection and staging of chronic liver diseases with a protein MRI contrast agent
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DOI：
10.1038/s41467-019-11984-2
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发表时间：
2019-10-29
影响因子：
16.6
通讯作者：
Yang, Jenny J.
中科院分区：
文献类型：
--
作者：
Salarian, Mani;Turaga, Ravi Chakra;Yang, Jenny J.
肝纤维化及其异质性的早期诊断和非侵入性检测仍然是阻止疾病进一步发展为严重临床后果的主要未满足的医疗需求。在这里，我们报告了一种I型胶原蛋白靶向蛋白质造影剂（ProCA32.collagen1），具有很强的I型胶原蛋白亲和力。ProCA32.collagen1在1.4和7.0 T下均具有高的每个颗粒弛豫率（r（1）和r（2）），这使得能够通过双对比模式在动物模型中稳健检测早期（Ishak 3/6期）肝纤维化和非酒精性脂肪性肝炎（Ishak 1/6期或1A轻度）。ProCA32.collagen1还通过系列分子成像证实了与肝内血管生成和晚期纤维化期间门脉高压相关的血管系统变化以及异质性。ProCA32.collagen1减轻了金属毒性，这是由于较低的剂量和对transmetabolism的强抗性以及对Gd 3+的前所未有的金属选择性超过生理金属离子，具有强的翻译潜力，有助于有效治疗以阻止进一步的慢性肝病进展。
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 (r(1) and r(2)) 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.