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Non-invasive molecular imaging of inflammatory macrophages in allograft rejection

BACKGROUND: Macrophages represent a critical cell type in host defense, development and homeostasis. The ability to image non-invasively pro-inflammatory macrophage infiltrate into a transplanted organ may provide an additional tool for the monitoring of the immune response of the recipient against...

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Autores principales: O’Neill, Alexander S. G., Terry, Samantha Y. A., Brown, Kathryn, Meader, Lucy, Wong, Andrew M. S., Cooper, Jonathan D., Crocker, Paul R., Wong, Wilson, Mullen, Gregory E. D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661159/
https://www.ncbi.nlm.nih.gov/pubmed/26611870
http://dx.doi.org/10.1186/s13550-015-0146-7
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author O’Neill, Alexander S. G.
Terry, Samantha Y. A.
Brown, Kathryn
Meader, Lucy
Wong, Andrew M. S.
Cooper, Jonathan D.
Crocker, Paul R.
Wong, Wilson
Mullen, Gregory E. D.
author_facet O’Neill, Alexander S. G.
Terry, Samantha Y. A.
Brown, Kathryn
Meader, Lucy
Wong, Andrew M. S.
Cooper, Jonathan D.
Crocker, Paul R.
Wong, Wilson
Mullen, Gregory E. D.
author_sort O’Neill, Alexander S. G.
collection PubMed
description BACKGROUND: Macrophages represent a critical cell type in host defense, development and homeostasis. The ability to image non-invasively pro-inflammatory macrophage infiltrate into a transplanted organ may provide an additional tool for the monitoring of the immune response of the recipient against the donor graft. We therefore decided to image in vivo sialoadhesin (Sn, Siglec 1 or CD169) using anti-Sn mAb (SER-4) directly radiolabelled with (99m)Tc pertechnetate. METHODS: We used a heterotopic heart transplantation model where allogeneic or syngeneic heart grafts were transplanted into the abdomen of recipients. In vivo nanosingle-photon emission computed tomography (SPECT/CT) imaging was performed 7 days post transplantation followed by biodistribution and histology. RESULTS: In wild-type mice, the majority of (99m)Tc-SER-4 monoclonal antibody cleared from the blood with a half-life of 167 min and was located predominantly on Sn(+) tissues in the spleen, liver and bone marrow. The biodistribution in the transplantation experiments confirmed data derived from the non-invasive SPECT/CT images, with significantly higher levels of (99m)Tc-SER-4 observed in allogeneic grafts (9.4 (±2.7) %ID/g) compared to syngeneic grafts (4.3 (±10.3) %ID/g) (p = 0.0022) or in mice which received allogeneic grafts injected with (99m)Tc-IgG isotype control (5.9 (±0.6) %ID/g) (p = 0.0185). The transplanted heart to blood ratio was also significantly higher in recipients with allogeneic grafts receiving (99m)Tc-SER-4 as compared to recipients with syngeneic grafts (p = 0.000004) or recipients with allogeneic grafts receiving (99m)Tc-IgG isotype (p = 0.000002). CONCLUSIONS: Here, we demonstrate that imaging of Sn(+) macrophages in inflammation may provide an important additional and non-invasive tool for the monitoring of the pathophysiology of cellular immunity in a transplant model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-015-0146-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-46611592015-12-04 Non-invasive molecular imaging of inflammatory macrophages in allograft rejection O’Neill, Alexander S. G. Terry, Samantha Y. A. Brown, Kathryn Meader, Lucy Wong, Andrew M. S. Cooper, Jonathan D. Crocker, Paul R. Wong, Wilson Mullen, Gregory E. D. EJNMMI Res Original Research BACKGROUND: Macrophages represent a critical cell type in host defense, development and homeostasis. The ability to image non-invasively pro-inflammatory macrophage infiltrate into a transplanted organ may provide an additional tool for the monitoring of the immune response of the recipient against the donor graft. We therefore decided to image in vivo sialoadhesin (Sn, Siglec 1 or CD169) using anti-Sn mAb (SER-4) directly radiolabelled with (99m)Tc pertechnetate. METHODS: We used a heterotopic heart transplantation model where allogeneic or syngeneic heart grafts were transplanted into the abdomen of recipients. In vivo nanosingle-photon emission computed tomography (SPECT/CT) imaging was performed 7 days post transplantation followed by biodistribution and histology. RESULTS: In wild-type mice, the majority of (99m)Tc-SER-4 monoclonal antibody cleared from the blood with a half-life of 167 min and was located predominantly on Sn(+) tissues in the spleen, liver and bone marrow. The biodistribution in the transplantation experiments confirmed data derived from the non-invasive SPECT/CT images, with significantly higher levels of (99m)Tc-SER-4 observed in allogeneic grafts (9.4 (±2.7) %ID/g) compared to syngeneic grafts (4.3 (±10.3) %ID/g) (p = 0.0022) or in mice which received allogeneic grafts injected with (99m)Tc-IgG isotype control (5.9 (±0.6) %ID/g) (p = 0.0185). The transplanted heart to blood ratio was also significantly higher in recipients with allogeneic grafts receiving (99m)Tc-SER-4 as compared to recipients with syngeneic grafts (p = 0.000004) or recipients with allogeneic grafts receiving (99m)Tc-IgG isotype (p = 0.000002). CONCLUSIONS: Here, we demonstrate that imaging of Sn(+) macrophages in inflammation may provide an important additional and non-invasive tool for the monitoring of the pathophysiology of cellular immunity in a transplant model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13550-015-0146-7) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2015-11-26 /pmc/articles/PMC4661159/ /pubmed/26611870 http://dx.doi.org/10.1186/s13550-015-0146-7 Text en © O’Neill et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
O’Neill, Alexander S. G.
Terry, Samantha Y. A.
Brown, Kathryn
Meader, Lucy
Wong, Andrew M. S.
Cooper, Jonathan D.
Crocker, Paul R.
Wong, Wilson
Mullen, Gregory E. D.
Non-invasive molecular imaging of inflammatory macrophages in allograft rejection
title Non-invasive molecular imaging of inflammatory macrophages in allograft rejection
title_full Non-invasive molecular imaging of inflammatory macrophages in allograft rejection
title_fullStr Non-invasive molecular imaging of inflammatory macrophages in allograft rejection
title_full_unstemmed Non-invasive molecular imaging of inflammatory macrophages in allograft rejection
title_short Non-invasive molecular imaging of inflammatory macrophages in allograft rejection
title_sort non-invasive molecular imaging of inflammatory macrophages in allograft rejection
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661159/
https://www.ncbi.nlm.nih.gov/pubmed/26611870
http://dx.doi.org/10.1186/s13550-015-0146-7
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