Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents
<h4>Background</h4> 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 osteoar...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089912/?tool=EBI |
| _version_ | 1818005974524362752 |
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| author | Milan M. Fowkes Patricia Das Neves Borges Fernando Cacho-Nerin Paul E. Brennan Tonia L. Vincent Ngee H. Lim |
| author_facet | Milan M. Fowkes Patricia Das Neves Borges Fernando Cacho-Nerin Paul E. Brennan Tonia L. Vincent Ngee H. Lim |
| author_sort | Milan M. Fowkes |
| collection | DOAJ |
| description | <h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusion</h4> DIPIC has reduction and refinement implications in OA animal research and potential clinical translation to imaging human disease. |
| first_indexed | 2024-04-14T04:53:58Z |
| format | Article |
| id | doaj.art-8a1747c88b8b40939436d491dd55283f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T04:53:58Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8a1747c88b8b40939436d491dd55283f2022-12-22T02:11:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01175Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agentsMilan M. FowkesPatricia Das Neves BorgesFernando Cacho-NerinPaul E. BrennanTonia L. VincentNgee H. Lim<h4>Background</h4> 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. <h4>Methods</h4> 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. <h4>Results</h4> 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. <h4>Conclusion</h4> DIPIC has reduction and refinement implications in OA animal research and potential clinical translation to imaging human disease.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089912/?tool=EBI |
| spellingShingle | Milan M. Fowkes Patricia Das Neves Borges Fernando Cacho-Nerin Paul E. Brennan Tonia L. Vincent Ngee H. Lim Imaging articular cartilage in osteoarthritis using targeted peptide radiocontrast agents PLoS ONE |
| 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 |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089912/?tool=EBI |
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