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Improving the reactivity of hydrazine-bearing MRI probes for in vivo imaging of lung fibrogenesis
Pulmonary fibrosis (PF) is the pathologic accumulation of extracellular matrix components in lung tissue that result in scarring following chronic lung injury. PF is typically diagnosed by high resolution computed tomography (HRCT) and/or invasive biopsy. However, HRCT cannot distinguish old injury...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362876/ https://www.ncbi.nlm.nih.gov/pubmed/32728411 http://dx.doi.org/10.1039/c9sc04821a |
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author | Akam, Eman A. Abston, Eric Rotile, Nicholas J. Slattery, Hannah R. Zhou, Iris Y. Lanuti, Michael Caravan, Peter |
author_facet | Akam, Eman A. Abston, Eric Rotile, Nicholas J. Slattery, Hannah R. Zhou, Iris Y. Lanuti, Michael Caravan, Peter |
author_sort | Akam, Eman A. |
collection | PubMed |
description | Pulmonary fibrosis (PF) is the pathologic accumulation of extracellular matrix components in lung tissue that result in scarring following chronic lung injury. PF is typically diagnosed by high resolution computed tomography (HRCT) and/or invasive biopsy. However, HRCT cannot distinguish old injury from active fibrogenesis. We previously demonstrated that allysine residues on oxidized collagen represent an abundant target during lung fibrogenesis, and that magnetic resonance imaging (MRI) with a small-molecule, gadolinium-containing probe, Gd-Hyd, could specifically detect and stage fibrogenesis in a mouse model. In this work, we present an improved probe, Gd-CHyd, featuring an N,N-dialkyl hydrazine which has an order of magnitude both greater reactivity and affinity for aldehydes. In a paired study in mice with bleomycin induced lung injury we show that the improved reactivity and affinity of Gd-CHyd results in significantly higher lung-to-liver contrast, e.g. 77% higher at 45 min post injection, and slower lung clearance than Gd-Hyd. Gd-CHyd enhanced MRI is >60-fold higher in bleomycin injured mouse lungs compared to uninjured mice. Collectively, our data indicate that enhancing hydrazine reactivity and affinity towards allysine is an effective strategy to significantly improve molecular MRI probes for lung fibrogenesis. |
format | Online Article Text |
id | pubmed-7362876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-73628762020-07-28 Improving the reactivity of hydrazine-bearing MRI probes for in vivo imaging of lung fibrogenesis Akam, Eman A. Abston, Eric Rotile, Nicholas J. Slattery, Hannah R. Zhou, Iris Y. Lanuti, Michael Caravan, Peter Chem Sci Chemistry Pulmonary fibrosis (PF) is the pathologic accumulation of extracellular matrix components in lung tissue that result in scarring following chronic lung injury. PF is typically diagnosed by high resolution computed tomography (HRCT) and/or invasive biopsy. However, HRCT cannot distinguish old injury from active fibrogenesis. We previously demonstrated that allysine residues on oxidized collagen represent an abundant target during lung fibrogenesis, and that magnetic resonance imaging (MRI) with a small-molecule, gadolinium-containing probe, Gd-Hyd, could specifically detect and stage fibrogenesis in a mouse model. In this work, we present an improved probe, Gd-CHyd, featuring an N,N-dialkyl hydrazine which has an order of magnitude both greater reactivity and affinity for aldehydes. In a paired study in mice with bleomycin induced lung injury we show that the improved reactivity and affinity of Gd-CHyd results in significantly higher lung-to-liver contrast, e.g. 77% higher at 45 min post injection, and slower lung clearance than Gd-Hyd. Gd-CHyd enhanced MRI is >60-fold higher in bleomycin injured mouse lungs compared to uninjured mice. Collectively, our data indicate that enhancing hydrazine reactivity and affinity towards allysine is an effective strategy to significantly improve molecular MRI probes for lung fibrogenesis. Royal Society of Chemistry 2019-11-08 /pmc/articles/PMC7362876/ /pubmed/32728411 http://dx.doi.org/10.1039/c9sc04821a Text en This journal is © The Royal Society of Chemistry 2020 http://creativecommons.org/licenses/by-nc/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported Licence (CC BY-NC 3.0) |
spellingShingle | Chemistry Akam, Eman A. Abston, Eric Rotile, Nicholas J. Slattery, Hannah R. Zhou, Iris Y. Lanuti, Michael Caravan, Peter Improving the reactivity of hydrazine-bearing MRI probes for in vivo imaging of lung fibrogenesis |
title | Improving the reactivity of hydrazine-bearing MRI probes for in vivo imaging of lung fibrogenesis
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title_full | Improving the reactivity of hydrazine-bearing MRI probes for in vivo imaging of lung fibrogenesis
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title_fullStr | Improving the reactivity of hydrazine-bearing MRI probes for in vivo imaging of lung fibrogenesis
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title_full_unstemmed | Improving the reactivity of hydrazine-bearing MRI probes for in vivo imaging of lung fibrogenesis
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title_short | Improving the reactivity of hydrazine-bearing MRI probes for in vivo imaging of lung fibrogenesis
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title_sort | improving the reactivity of hydrazine-bearing mri probes for in vivo imaging of lung fibrogenesis |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362876/ https://www.ncbi.nlm.nih.gov/pubmed/32728411 http://dx.doi.org/10.1039/c9sc04821a |
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