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Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents

BACKGROUND: Established MRI and emerging X-ray contrast agents for non-invasive imaging of articular cartilage rely on non-selective electrostatic interactions with negatively charged proteoglycans. These contrast agents have limited prognostic utility in diseases such as osteoarthritis (OA) due to...

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Autores principales: Fowkes, Milan M., Das Neves Borges, Patricia, Cacho-Nerin, Fernando, Brennan, Paul E., Vincent, Tonia L., Lim, Ngee H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089912/
https://www.ncbi.nlm.nih.gov/pubmed/35536857
http://dx.doi.org/10.1371/journal.pone.0268223
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author Fowkes, Milan M.
Das Neves Borges, Patricia
Cacho-Nerin, Fernando
Brennan, Paul E.
Vincent, Tonia L.
Lim, Ngee H.
author_facet Fowkes, Milan M.
Das Neves Borges, Patricia
Cacho-Nerin, Fernando
Brennan, Paul E.
Vincent, Tonia L.
Lim, Ngee H.
author_sort Fowkes, Milan M.
collection PubMed
description BACKGROUND: Established MRI and emerging X-ray contrast agents for non-invasive imaging of articular cartilage rely on non-selective electrostatic interactions with negatively charged proteoglycans. These contrast agents have limited prognostic utility in diseases such as osteoarthritis (OA) due to the characteristic high turnover of proteoglycans. To overcome this limitation, we developed a radiocontrast agent that targets the type II collagen macromolecule in cartilage and used it to monitor disease progression in a murine model of OA. METHODS: To confer radiopacity to cartilage contrast agents, the naturally occurring tyrosine derivative 3,5-diiodo-L-tyrosine (DIT) was introduced into a selective peptide for type II collagen. Synthetic DIT peptide derivatives were synthesised by Fmoc-based solid-phase peptide synthesis and binding to ex vivo mouse tibial cartilage evaluated by high-resolution micro-CT. Di-Iodotyrosinated Peptide Imaging of Cartilage (DIPIC) was performed ex vivo and in vivo 4, 8 and 12 weeks in mice after induction of OA by destabilisation of the medial meniscus (DMM). Finally, human osteochondral plugs were imaged ex vivo using DIPIC. RESULTS: Fifteen DIT peptides were synthesised and tested, yielding seven leads with varying cartilage binding strengths. DIPIC visualised ex vivo murine articular cartilage comparably to the ex vivo contrast agent phosphotungstic acid. Intra-articular injection of contrast agent followed by in vivo DIPIC enabled delineation of damaged murine articular cartilage. Finally, the translational potential of the contrast agent was confirmed by visualisation of ex vivo human cartilage explants. CONCLUSION: DIPIC has reduction and refinement implications in OA animal research and potential clinical translation to imaging human disease.
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spelling pubmed-90899122022-05-11 Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents Fowkes, Milan M. Das Neves Borges, Patricia Cacho-Nerin, Fernando Brennan, Paul E. Vincent, Tonia L. Lim, Ngee H. PLoS One Research Article BACKGROUND: Established MRI and emerging X-ray contrast agents for non-invasive imaging of articular cartilage rely on non-selective electrostatic interactions with negatively charged proteoglycans. These contrast agents have limited prognostic utility in diseases such as osteoarthritis (OA) due to the characteristic high turnover of proteoglycans. To overcome this limitation, we developed a radiocontrast agent that targets the type II collagen macromolecule in cartilage and used it to monitor disease progression in a murine model of OA. METHODS: To confer radiopacity to cartilage contrast agents, the naturally occurring tyrosine derivative 3,5-diiodo-L-tyrosine (DIT) was introduced into a selective peptide for type II collagen. Synthetic DIT peptide derivatives were synthesised by Fmoc-based solid-phase peptide synthesis and binding to ex vivo mouse tibial cartilage evaluated by high-resolution micro-CT. Di-Iodotyrosinated Peptide Imaging of Cartilage (DIPIC) was performed ex vivo and in vivo 4, 8 and 12 weeks in mice after induction of OA by destabilisation of the medial meniscus (DMM). Finally, human osteochondral plugs were imaged ex vivo using DIPIC. RESULTS: Fifteen DIT peptides were synthesised and tested, yielding seven leads with varying cartilage binding strengths. DIPIC visualised ex vivo murine articular cartilage comparably to the ex vivo contrast agent phosphotungstic acid. Intra-articular injection of contrast agent followed by in vivo DIPIC enabled delineation of damaged murine articular cartilage. Finally, the translational potential of the contrast agent was confirmed by visualisation of ex vivo human cartilage explants. CONCLUSION: DIPIC has reduction and refinement implications in OA animal research and potential clinical translation to imaging human disease. Public Library of Science 2022-05-10 /pmc/articles/PMC9089912/ /pubmed/35536857 http://dx.doi.org/10.1371/journal.pone.0268223 Text en © 2022 Fowkes et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Fowkes, Milan M.
Das Neves Borges, Patricia
Cacho-Nerin, Fernando
Brennan, Paul E.
Vincent, Tonia L.
Lim, Ngee H.
Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents
title Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents
title_full Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents
title_fullStr Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents
title_full_unstemmed Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents
title_short Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents
title_sort imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089912/
https://www.ncbi.nlm.nih.gov/pubmed/35536857
http://dx.doi.org/10.1371/journal.pone.0268223
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