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dc.contributor.author | González, María Isabel | |
dc.contributor.author | González-Arjona, Mario | |
dc.contributor.author | Cusso, Lorena | |
dc.contributor.author | Morcillo, Miguel Ángel | |
dc.contributor.author | Aguilera-Correa, John Jairo | |
dc.contributor.author | Esteban, Jaime | |
dc.contributor.author | Kestler, Martha | |
dc.contributor.author | Calle, Daniel | |
dc.contributor.author | Cerón, Carlos | |
dc.contributor.author | Cortes-Canteli, Marta | |
dc.contributor.author | Muñoz, Patricia | |
dc.contributor.author | Bouza, Emilio | |
dc.contributor.author | Desco, Manuel | |
dc.contributor.author | Salinas, Beatriz | |
dc.date.accessioned | 2024-07-02T13:03:21Z | |
dc.date.available | 2024-07-02T13:03:21Z | |
dc.date.issued | 2024 | |
dc.identifier.citation | Int J Biomed Imaging. 2024 Apr 18:2024:3655327 | es_ES |
dc.identifier.issn | 1687-4188 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/19911 | |
dc.description.abstract | PURPOSE The Gram-positive Staphylococcus aureus bacterium is one of the leading causes of infection in humans. The lack of specific noninvasive techniques for diagnosis of staphylococcal infection together with the severity of its associated complications support the need for new specific and selective diagnostic tools. This work presents the successful synthesis of an immunotracer that targets the α-toxin released by S. aureus. METHODS [89Zr]Zr-DFO-ToxAb was synthesized based on radiolabeling an anti-α-toxin antibody with zirconium-89. The physicochemical characterization of the immunotracer was performed by high-performance liquid chromatography (HPLC), radio-thin layer chromatography (radio-TLC), and electrophoretic analysis. Its diagnostic ability was evaluated in vivo by positron emission tomography/computed tomography (PET/CT) imaging in an animal model of local infection-inflammation (active S. aureus vs. heat-killed S. aureus) and infective osteoarthritis. RESULTS Chemical characterization of the tracer established the high radiochemical yield and purity of the tracer while maintaining antibody integrity. In vivo PET/CT image confirmed the ability of the tracer to detect active foci of S. aureus. Those results were supported by ex vivo biodistribution studies, autoradiography, and histology, which confirmed the ability of [89Zr]Zr-DFO-ToxAb to detect staphylococcal infectious foci, avoiding false-positives derived from inflammatory processes. CONCLUSIONS We have developed an immuno-PET tracer capable of detecting S. aureus infections based on a radiolabeled antibody specific for the staphylococcal alpha toxins. The in vivo assessment of [89Zr]Zr-DFO-ToxAb confirmed its ability to selectively detect staphylococcal infectious foci, allowing us to discern between infectious and inflammatory processes. | es_ES |
dc.description.sponsorship | This study was funded by the Instituto de Salud Carlos III through projects PI20/01632, PT20/00044, and PI23/01405, cofunded by the European Regional Development Fund (ERDF), “A way to make Europe”; by the Fundación Ramón Areces; and by the Comunidad de Madrid, project “S2022/ BMD-7403 RENIM-CM.” This work was also supported by “Diagnosis and treatment follow-up of severe staphylococcal infections with anti-staphylococcal antibodies and immunePET—Grant Fundación BBVA a Equipos de Investigación Científica 2018” and by Grant EQC2019-006674-P funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe.” M.C.-C. is funded by a Miguel Servet type II research contract (CPII21/00007) from the Instituto de Salud Carlos III, Madrid, Spain. C.C. is funded by a predoctoral fellowship from the Fundación Española de Trombosis y Hemostasia (FETH-SETH). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCNI), and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence. The authors thank Gorka Sobrino from the Unidad de Imagen Avanzada of Centro Nacional de Investigaciones Cardiovasculares (CNIC) Carlos III for assistance with the HPLC and gamma counter equipment; Yolanda Sierra, Alexandra de Francisco, and María de la Jara Felipe from the Imaging Laboratory for Small Animal Experimentation of Instituto de Investigación Sanitaria Gregorio Marañón for their excellent work with animal preparation and imaging protocols; and Roisin Brid Doohan, Claudio Badía Careaga, and Dr. Antonio de Molina from the Histopathology Unit of Centro Nacional de Investigaciones Cardiovasculares (CNIC) Carlos III for the histological sample treatments and histopathological analyses. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Hindawi | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | In Vivo Detection of Staphylococcus aureus Infections Using Radiolabeled Antibodies Specific for Bacterial Toxins. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 38665417 | es_ES |
dc.format.volume | 2024 | es_ES |
dc.format.page | 3655327 | es_ES |
dc.identifier.doi | 10.1155/2024/3655327 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Fundación Ramón Areces | es_ES |
dc.contributor.funder | Comunidad de Madrid (España) | es_ES |
dc.contributor.funder | Fundación BBVA | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Fundación ProCNIC | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.relation.publisherversion | 10.1155/2024/3655327 | es_ES |
dc.identifier.journal | International journal of biomedical imaging | es_ES |
dc.repisalud.orgCNIC | CNIC::Unidades técnicas::Imagen Avanzada | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI20/01632 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PT20/00044 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI23/01405 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/S2022/BMD-7403-RENIM-CM | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/EQC2019-006674-P | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/MCIN/AEI/10.13039/501100011033 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/CPII21/00007 | es_ES |