PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease model
Monoclonal antibodies targeting tumor necrosis factor-alpha (antiTNF-α) are used for patients with immuno-mediated illness as inflammatory bowel disease (IBD). However, 20–40 % of IBD patients do not respond to these therapies, and increasing knowledge of biodistribution could optimize their use and...
| Autores: | , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión enviada para evaluación y publicación |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/419993 |
| Acceso en línea: | http://hdl.handle.net/10261/419993 https://api.elsevier.com/content/abstract/scopus_id/85211493009 |
| Access Level: | acceso abierto |
| Palabra clave: | AntiTNF-α Adalimumab ImmunoPET Inflammatory bowel disease Intravenous administration Subcutaneous administration |
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PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease modelCodesido, JessicaGarcía-Varela, LaraGarcía-Otero, XurxoBouzón-Barreiro, SheilaGómez-Lado, NoemíToja-Camba, Francisco JoséMondelo-García, CristinaLazaré, HéctorBaguña Torres, JúliaVidal-Otero, JanaMedin-Aguerre, SantiagoSanchez-Crespo, AlejandroOtero-Espinar, Francisco J.Herance, José R.Fernández-Ferreiro, AnxoAguiar, PabloAntiTNF-αAdalimumabImmunoPETInflammatory bowel diseaseIntravenous administrationSubcutaneous administrationMonoclonal antibodies targeting tumor necrosis factor-alpha (antiTNF-α) are used for patients with immuno-mediated illness as inflammatory bowel disease (IBD). However, 20–40 % of IBD patients do not respond to these therapies, and increasing knowledge of biodistribution could optimize their use and consequently their effectiveness. The aim of this study is to compare the biodistribution of adalimumab after intravenous (IV) and subcutaneous (SC) administration using Positron Emission Tomography (PET) imaging in IBD animal models. IBD was induced in mice using oral dextran sulfate sodium (DSS) and each induced animal was individually confirmed using [18F]FDG PET/CT scans, weight monitoring and histopathological analysis of colon tissue samples. The SC and IV biodistribution pharmacokinetics profiles and in vivo biodistribution of adalimumab labeled with 89Zr were evaluated using a dedicated PET/CT scanner. Mean standardized uptake values (SUV) were estimated from the colon, liver, and blood over seven days. Blood analysis revealed faster elimination of adalimumab in IBD models compared to controls, and after IV compared to SC administration (SUV 168 h p.i. SC-IBD = 0.06 ± 0.02, SC-Control = 1.08 ± 0.11, IV-IBD = 0.02 ± 0.01, IV-Control = 0.26 ± 0.13). Furthermore, IBD models exhibited faster whole-body clearance than controls and an earlier and higher concentration peak of adalimumab in the colon after IV (SUV 6 h p.i. IBD-IV = 2.11 ± 0.18) compared to SC administration (SUV 24 h p.i. IBD-SC = 1.49 ± 0.27). Our findings demonstrate the significant influence of the administration route and the TNF-α expression (local and also systemic) on the amount of adalimumab reaching the colon over time.This work was partially supported by Instituto de Salud Carlos III (ISCIII, Spain) through PI20/00719 project, Axencia Galega de Innovacion (Grupos de Potencial Crecimiento IN607B2020/11, Spain), Ministry of Science and Innovation of Spain (MICINN, Spain) through PID2022-138183OB-I00 project. J. Codesido is grateful to the Health Research Institute of Santiago de Compostela (IDIS, Spain) for financing his predoctoral research fellowship and X. García-Otero acknowledges the support of Xunta de Galicia (Spain) through the postdoctoral fellowship [ED481B-2023-063].NoElsevierInstituto de Salud Carlos IIIAxencia Galega de InnovaciónMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Xunta de Galicia202620262025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Preprintinfo:eu-repo/semantics/submittedVersionapplication/pdfhttp://hdl.handle.net/10261/419993https://api.elsevier.com/content/abstract/scopus_id/85211493009reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-138183OB-I00https://doi.org/10.1016/j.ijpharm.2024.125011Noinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4199932026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease model |
| title |
PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease model |
| spellingShingle |
PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease model Codesido, Jessica AntiTNF-α Adalimumab ImmunoPET Inflammatory bowel disease Intravenous administration Subcutaneous administration |
| title_short |
PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease model |
| title_full |
PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease model |
| title_fullStr |
PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease model |
| title_full_unstemmed |
PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease model |
| title_sort |
PET biodistribution study of subcutaneous and intravenous administration of adalimumab in an inflammatory bowel disease model |
| dc.creator.none.fl_str_mv |
Codesido, Jessica García-Varela, Lara García-Otero, Xurxo Bouzón-Barreiro, Sheila Gómez-Lado, Noemí Toja-Camba, Francisco José Mondelo-García, Cristina Lazaré, Héctor Baguña Torres, Júlia Vidal-Otero, Jana Medin-Aguerre, Santiago Sanchez-Crespo, Alejandro Otero-Espinar, Francisco J. Herance, José R. Fernández-Ferreiro, Anxo Aguiar, Pablo |
| author |
Codesido, Jessica |
| author_facet |
Codesido, Jessica García-Varela, Lara García-Otero, Xurxo Bouzón-Barreiro, Sheila Gómez-Lado, Noemí Toja-Camba, Francisco José Mondelo-García, Cristina Lazaré, Héctor Baguña Torres, Júlia Vidal-Otero, Jana Medin-Aguerre, Santiago Sanchez-Crespo, Alejandro Otero-Espinar, Francisco J. Herance, José R. Fernández-Ferreiro, Anxo Aguiar, Pablo |
| author_role |
author |
| author2 |
García-Varela, Lara García-Otero, Xurxo Bouzón-Barreiro, Sheila Gómez-Lado, Noemí Toja-Camba, Francisco José Mondelo-García, Cristina Lazaré, Héctor Baguña Torres, Júlia Vidal-Otero, Jana Medin-Aguerre, Santiago Sanchez-Crespo, Alejandro Otero-Espinar, Francisco J. Herance, José R. Fernández-Ferreiro, Anxo Aguiar, Pablo |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Instituto de Salud Carlos III Axencia Galega de Innovación Ministerio de Ciencia e Innovación (España) Agencia Estatal de Investigación (España) Xunta de Galicia |
| dc.subject.none.fl_str_mv |
AntiTNF-α Adalimumab ImmunoPET Inflammatory bowel disease Intravenous administration Subcutaneous administration |
| topic |
AntiTNF-α Adalimumab ImmunoPET Inflammatory bowel disease Intravenous administration Subcutaneous administration |
| description |
Monoclonal antibodies targeting tumor necrosis factor-alpha (antiTNF-α) are used for patients with immuno-mediated illness as inflammatory bowel disease (IBD). However, 20–40 % of IBD patients do not respond to these therapies, and increasing knowledge of biodistribution could optimize their use and consequently their effectiveness. The aim of this study is to compare the biodistribution of adalimumab after intravenous (IV) and subcutaneous (SC) administration using Positron Emission Tomography (PET) imaging in IBD animal models. IBD was induced in mice using oral dextran sulfate sodium (DSS) and each induced animal was individually confirmed using [18F]FDG PET/CT scans, weight monitoring and histopathological analysis of colon tissue samples. The SC and IV biodistribution pharmacokinetics profiles and in vivo biodistribution of adalimumab labeled with 89Zr were evaluated using a dedicated PET/CT scanner. Mean standardized uptake values (SUV) were estimated from the colon, liver, and blood over seven days. Blood analysis revealed faster elimination of adalimumab in IBD models compared to controls, and after IV compared to SC administration (SUV 168 h p.i. SC-IBD = 0.06 ± 0.02, SC-Control = 1.08 ± 0.11, IV-IBD = 0.02 ± 0.01, IV-Control = 0.26 ± 0.13). Furthermore, IBD models exhibited faster whole-body clearance than controls and an earlier and higher concentration peak of adalimumab in the colon after IV (SUV 6 h p.i. IBD-IV = 2.11 ± 0.18) compared to SC administration (SUV 24 h p.i. IBD-SC = 1.49 ± 0.27). Our findings demonstrate the significant influence of the administration route and the TNF-α expression (local and also systemic) on the amount of adalimumab reaching the colon over time. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 2026 2026 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Preprint info:eu-repo/semantics/submittedVersion |
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article |
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submittedVersion |
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http://hdl.handle.net/10261/419993 https://api.elsevier.com/content/abstract/scopus_id/85211493009 |
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http://hdl.handle.net/10261/419993 https://api.elsevier.com/content/abstract/scopus_id/85211493009 |
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Inglés |
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Inglés |
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#PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-138183OB-I00 https://doi.org/10.1016/j.ijpharm.2024.125011 No |
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