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https://hdl.handle.net/2440/129908
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Type: | Journal article |
Title: | ⁸⁹Zr-pro-MMP-9 F(ab′)₂ detects colitis induced intestinal and kidney fibrosis |
Other Titles: | (89)Zr-pro-MMP-9 F(ab')(2) detects colitis induced intestinal and kidney fibrosis |
Author: | Dmochowska, N. Tieu, W. Keller, M.D. Hollis, C.A. Campaniello, M.A. Mavrangelos, C. Takhar, P. Hughes, P.A. |
Citation: | Scientific Reports, 2020; 10(1):20372-20372 |
Publisher: | Springer Science and Business Media LLC |
Issue Date: | 2020 |
ISSN: | 2045-2322 2045-2322 |
Statement of Responsibility: | Nicole Dmochowska, William Tieu, Marianne D. Keller, Courtney A. Hollis, Melissa A. Campaniello, Chris Mavrangelos, Prab Takhar and Patrick A. Hughes |
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. |
Keywords: | Colon Kidney Feces Animals Mice, Inbred C57BL Mice, Transgenic Mice Colitis Fibrosis Zirconium Radioisotopes Sodium Dodecyl Sulfate Collagen Enzyme Precursors Peroxidase Positron-Emission Tomography Magnetic Resonance Imaging Gene Expression Immunoglobulin Fab Fragments Male Matrix Metalloproteinase 9 |
Rights: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
DOI: | 10.1038/s41598-020-77390-7 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1105028 |
Published version: | http://dx.doi.org/10.1038/s41598-020-77390-7 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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