89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis

Abstract Intestinal fibrosis is a common complication of inflammatory bowel disease but remains difficult to detect. Matrix metalloproteases (MMPs) have key roles in fibrosis and are therefore potential targets for fibrosis detection. We determined whether immunoPET of F(ab′)2 antibody fragments tar...

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Autores principales:	Nicole Dmochowska, William Tieu, Marianne D. Keller, Courtney A. Hollis, Melissa A. Campaniello, Chris Mavrangelos, Prab Takhar, Patrick A. Hughes
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/37d95436984e45b4b6bac1118dadc677
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spelling	oai:doaj.org-article:37d95436984e45b4b6bac1118dadc6772021-12-02T15:10:24Z89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis10.1038/s41598-020-77390-72045-2322https://doaj.org/article/37d95436984e45b4b6bac1118dadc6772020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77390-7https://doaj.org/toc/2045-2322Abstract Intestinal fibrosis is a common complication of inflammatory bowel disease but remains difficult to detect. Matrix metalloproteases (MMPs) have key roles in fibrosis and are therefore potential targets for fibrosis detection. We determined whether immunoPET of F(ab′)2 antibody fragments targeting MMPs detects colitis induced colonic fibrosis. Mice were administered 2% dextran sulfate sodium treated water for 1 cycle (inflamed) or 3 cycles (fibrotic), or were untreated (control). Colonic and kidney collagen, innate cytokine, MMPs and fecal MPO concentrations were analyzed by multiplex/ELISA. α-pro-MMP-9 F(ab′)2 fragments were engineered and conjugated to 89Zr for PET imaging, ex-vivo Cherenkov analysis and bio-distribution. Colonic innate cytokine concentrations and fecal myeloperoxidase were increased in inflamed mice but not fibrotic mice, while collagen concentrations were increased in fibrotic mice. MMPs were increased in inflamed mice, but only pro-MMP-9 remained increased in fibrotic mice. 89Zr-pro-MMP-9 F(ab′)2 uptake was increased in the intestine but also in the kidney of fibrotic mice, where collagen and pro-MMP-9 concentrations were increased. 89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal fibrosis and associated kidney fibrosis.Nicole DmochowskaWilliam TieuMarianne D. KellerCourtney A. HollisMelissa A. CampanielloChris MavrangelosPrab TakharPatrick A. HughesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicole Dmochowska William Tieu Marianne D. Keller Courtney A. Hollis Melissa A. Campaniello Chris Mavrangelos Prab Takhar Patrick A. Hughes 89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis
description	Abstract Intestinal fibrosis is a common complication of inflammatory bowel disease but remains difficult to detect. Matrix metalloproteases (MMPs) have key roles in fibrosis and are therefore potential targets for fibrosis detection. We determined whether immunoPET of F(ab′)2 antibody fragments targeting MMPs detects colitis induced colonic fibrosis. Mice were administered 2% dextran sulfate sodium treated water for 1 cycle (inflamed) or 3 cycles (fibrotic), or were untreated (control). Colonic and kidney collagen, innate cytokine, MMPs and fecal MPO concentrations were analyzed by multiplex/ELISA. α-pro-MMP-9 F(ab′)2 fragments were engineered and conjugated to 89Zr for PET imaging, ex-vivo Cherenkov analysis and bio-distribution. Colonic innate cytokine concentrations and fecal myeloperoxidase were increased in inflamed mice but not fibrotic mice, while collagen concentrations were increased in fibrotic mice. MMPs were increased in inflamed mice, but only pro-MMP-9 remained increased in fibrotic mice. 89Zr-pro-MMP-9 F(ab′)2 uptake was increased in the intestine but also in the kidney of fibrotic mice, where collagen and pro-MMP-9 concentrations were increased. 89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal fibrosis and associated kidney fibrosis.
format	article
author	Nicole Dmochowska William Tieu Marianne D. Keller Courtney A. Hollis Melissa A. Campaniello Chris Mavrangelos Prab Takhar Patrick A. Hughes
author_facet	Nicole Dmochowska William Tieu Marianne D. Keller Courtney A. Hollis Melissa A. Campaniello Chris Mavrangelos Prab Takhar Patrick A. Hughes
author_sort	Nicole Dmochowska
title	89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis
title_short	89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis
title_full	89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis
title_fullStr	89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis
title_full_unstemmed	89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis
title_sort	89zr-pro-mmp-9 f(ab′)2 detects colitis induced intestinal and kidney fibrosis
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/37d95436984e45b4b6bac1118dadc677
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89Zr-pro-MMP-9 F(ab′)2 detects colitis induced intestinal and kidney fibrosis

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