Manganese-based type I collagen-targeting MRI probe for in vivo imaging of liver fibrosis

Manganese-based type I collagen-targeting MRI probe for in vivo imaging of liver fibrosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Manganese-based type I collagen-targeting MRI probe for in vivo imaging of liver fibrosis Chunxiang Zhang, Hua Ma, Daniel DeRoche, Eric M. Gale, Pamela Pantazopoulos, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5349052/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Apr, 2025 Read the published version in npj Imaging → Version 1 posted 9 You are reading this latest preprint version Abstract Liver fibrosis is a common pathway shared by all forms of progressive chronic liver disease. There is an unmet clinical need for noninvasive imaging tools to diagnose and stage fibrosis, which presently relies heavily on percutaneous liver biopsy. Here we explored the feasibility of using a novel type I collagen-targeted manganese (Mn)-based MRI probe, Mn-CBP20, for liver fibrosis imaging. In vitro characterization of Mn-CBP20 demonstrated its high binding affinity for human collagen (Kd = 9.6 µM), high T1-relaxivity (48.9 mM-1s-1 at 1.4T and 27°C), and kinetic inertness to Mn release under forcing conditions. We demonstrated MRI using Mn-CBP20 performs comparably to previously reported gadolinium-based type I collagen-targeted probe EP-3533 in a mouse model of carbon tetrachloride-induced liver fibrosis, and further demonstrate efficacy to detect fibrosis in a diet-induced mouse model of metabolically-associated steatohepatitis. Biodistribution studies using the Mn-CBP20 radio-labeled with the positron-emitting 52Mn isotope demonstrate efficient clearance of Mn-CBP20 primarily via renal excretion. Mn-CBP20 represents a promising candidate that merits further evaluation and development for molecular imaging of liver fibrosis. Health sciences/Diseases Biological sciences/Biological techniques/Imaging/Magnetic resonance imaging Health sciences/Health care/Medical imaging/Molecular imaging Physical sciences/Chemistry/Analytical chemistry/Imaging studies collagen manganese fibrosis molecular imaging MRI Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 08 Apr, 2025 Read the published version in npj Imaging → Version 1 posted Editorial decision: Revision requested 18 Nov, 2024 Reviews received at journal 18 Nov, 2024 Reviews received at journal 16 Nov, 2024 Reviewers agreed at journal 11 Nov, 2024 Reviewers agreed at journal 07 Nov, 2024 Reviewers invited by journal 07 Nov, 2024 Editor assigned by journal 07 Nov, 2024 Submission checks completed at journal 06 Nov, 2024 First submitted to journal 28 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5349052","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":379588935,"identity":"40d82699-1c23-4b44-a99c-cf9837a4a58a","order_by":0,"name":"Chunxiang Zhang","email":"","orcid":"","institution":"Athinoula A. 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There is an unmet clinical need for noninvasive imaging tools to diagnose and stage fibrosis, which presently relies heavily on percutaneous liver biopsy. Here we explored the feasibility of using a novel type I collagen-targeted manganese (Mn)-based MRI probe, Mn-CBP20, for liver fibrosis imaging. In vitro characterization of Mn-CBP20 demonstrated its high binding affinity for human collagen (Kd = 9.6 µM), high T1-relaxivity (48.9 mM-1s-1 at 1.4T and 27°C), and kinetic inertness to Mn release under forcing conditions. We demonstrated MRI using Mn-CBP20 performs comparably to previously reported gadolinium-based type I collagen-targeted probe EP-3533 in a mouse model of carbon tetrachloride-induced liver fibrosis, and further demonstrate efficacy to detect fibrosis in a diet-induced mouse model of metabolically-associated steatohepatitis. Biodistribution studies using the Mn-CBP20 radio-labeled with the positron-emitting 52Mn isotope demonstrate efficient clearance of Mn-CBP20 primarily via renal excretion. 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