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Radioimmune Imaging of α(4)β(7) Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease
Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to eval...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051745/ https://www.ncbi.nlm.nih.gov/pubmed/36986677 http://dx.doi.org/10.3390/pharmaceutics15030817 |
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author | Signore, Alberto Bonfiglio, Rita Varani, Michela Galli, Filippo Campagna, Giuseppe Desco, Manuel Cussó, Lorena Mattei, Maurizio Wunder, Andreas Borri, Filippo Lupo, Maria T. Bonanno, Elena |
author_facet | Signore, Alberto Bonfiglio, Rita Varani, Michela Galli, Filippo Campagna, Giuseppe Desco, Manuel Cussó, Lorena Mattei, Maurizio Wunder, Andreas Borri, Filippo Lupo, Maria T. Bonanno, Elena |
author_sort | Signore, Alberto |
collection | PubMed |
description | Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to evaluate if a pre-therapy scan with radiolabelled anti-α(4)β(7) integrin or radiolabelled anti-TNFα mAb could predict therapeutic outcome with unlabelled anti-α(4)β(7) integrin or anti-TNFα mAb. To this aim, we developed two radiopharmaceuticals to study the expression of therapeutic targets for inflammatory bowel diseases (IBD), to be used for therapy decision making. Both anti-α(4)β(7) integrin and anti-TNFα mAbs were successfully radiolabelled with technetium-99m with high labelling efficiency and stability. Dextran sulfate sodium (DSS)-induced colitis was used as a model for murine IBD and the bowel uptake of radiolabelled mAbs was evaluated ex vivo and in vivo by planar and SPECT/CT images. These studies allowed us to define best imaging strategy and to validate the specificity of mAb binding in vivo to their targets. Bowel uptake in four different regions was compared to immunohistochemistry (IHC) score (partial and global). Then, to evaluate the biomarker expression prior to therapy administration, in initial IBD, another group of DSS-treated mice was injected with radiolabelled mAb on day 2 of DSS administration (to quantify the presence of the target in the bowel) and then injected with a single therapeutic dose of unlabelled anti-α(4)β(7) integrin or anti-TNFα mAb. Good correlation was demonstrated between bowel uptake of radiolabelled mAb and immunohistochemistry (IHC) score, both in vivo and ex vivo. Mice treated with unlabelled α(4)β(7) integrin and anti-TNFα showed an inverse correlation between the bowel uptake of radiolabelled mAb and the histological score after therapy, proving that only mice with high α(4)β(7) integrin or TNFα expression will benefit of therapy with unlabelled mAb. |
format | Online Article Text |
id | pubmed-10051745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100517452023-03-30 Radioimmune Imaging of α(4)β(7) Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease Signore, Alberto Bonfiglio, Rita Varani, Michela Galli, Filippo Campagna, Giuseppe Desco, Manuel Cussó, Lorena Mattei, Maurizio Wunder, Andreas Borri, Filippo Lupo, Maria T. Bonanno, Elena Pharmaceutics Article Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to evaluate if a pre-therapy scan with radiolabelled anti-α(4)β(7) integrin or radiolabelled anti-TNFα mAb could predict therapeutic outcome with unlabelled anti-α(4)β(7) integrin or anti-TNFα mAb. To this aim, we developed two radiopharmaceuticals to study the expression of therapeutic targets for inflammatory bowel diseases (IBD), to be used for therapy decision making. Both anti-α(4)β(7) integrin and anti-TNFα mAbs were successfully radiolabelled with technetium-99m with high labelling efficiency and stability. Dextran sulfate sodium (DSS)-induced colitis was used as a model for murine IBD and the bowel uptake of radiolabelled mAbs was evaluated ex vivo and in vivo by planar and SPECT/CT images. These studies allowed us to define best imaging strategy and to validate the specificity of mAb binding in vivo to their targets. Bowel uptake in four different regions was compared to immunohistochemistry (IHC) score (partial and global). Then, to evaluate the biomarker expression prior to therapy administration, in initial IBD, another group of DSS-treated mice was injected with radiolabelled mAb on day 2 of DSS administration (to quantify the presence of the target in the bowel) and then injected with a single therapeutic dose of unlabelled anti-α(4)β(7) integrin or anti-TNFα mAb. Good correlation was demonstrated between bowel uptake of radiolabelled mAb and immunohistochemistry (IHC) score, both in vivo and ex vivo. Mice treated with unlabelled α(4)β(7) integrin and anti-TNFα showed an inverse correlation between the bowel uptake of radiolabelled mAb and the histological score after therapy, proving that only mice with high α(4)β(7) integrin or TNFα expression will benefit of therapy with unlabelled mAb. MDPI 2023-03-02 /pmc/articles/PMC10051745/ /pubmed/36986677 http://dx.doi.org/10.3390/pharmaceutics15030817 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Signore, Alberto Bonfiglio, Rita Varani, Michela Galli, Filippo Campagna, Giuseppe Desco, Manuel Cussó, Lorena Mattei, Maurizio Wunder, Andreas Borri, Filippo Lupo, Maria T. Bonanno, Elena Radioimmune Imaging of α(4)β(7) Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease |
title | Radioimmune Imaging of α(4)β(7) Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease |
title_full | Radioimmune Imaging of α(4)β(7) Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease |
title_fullStr | Radioimmune Imaging of α(4)β(7) Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease |
title_full_unstemmed | Radioimmune Imaging of α(4)β(7) Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease |
title_short | Radioimmune Imaging of α(4)β(7) Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease |
title_sort | radioimmune imaging of α(4)β(7) integrin and tnfα for diagnostic and therapeutic applications in inflammatory bowel disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051745/ https://www.ncbi.nlm.nih.gov/pubmed/36986677 http://dx.doi.org/10.3390/pharmaceutics15030817 |
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