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Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach

PURPOSE: Atherosclerotic plaque development and progression signifies a complex inflammatory disease mediated by a multitude of proinflammatory leukocyte subsets. Using single photon emission computed tomography (SPECT) coupled with computed tomography (CT), this study tested a new dual-isotope acqu...

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Autores principales: Barrett, Hilary E., Meester, Eric J., van Gaalen, Kim, van der Heiden, Kim, Krenning, Boudewijn J., Beekman, Freek J., de Blois, Erik, de Swart, Jan, Verhagen, H J, Maina, Theodosia, Nock, Berthold A., Norenberg, Jeffrey P., de Jong, Marion, Gijsen, Frank J. H., Bernsen, Monique R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567726/
https://www.ncbi.nlm.nih.gov/pubmed/32291511
http://dx.doi.org/10.1007/s00259-020-04776-0
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author Barrett, Hilary E.
Meester, Eric J.
van Gaalen, Kim
van der Heiden, Kim
Krenning, Boudewijn J.
Beekman, Freek J.
de Blois, Erik
de Swart, Jan
Verhagen, H J
Maina, Theodosia
Nock, Berthold A.
Norenberg, Jeffrey P.
de Jong, Marion
Gijsen, Frank J. H.
Bernsen, Monique R.
author_facet Barrett, Hilary E.
Meester, Eric J.
van Gaalen, Kim
van der Heiden, Kim
Krenning, Boudewijn J.
Beekman, Freek J.
de Blois, Erik
de Swart, Jan
Verhagen, H J
Maina, Theodosia
Nock, Berthold A.
Norenberg, Jeffrey P.
de Jong, Marion
Gijsen, Frank J. H.
Bernsen, Monique R.
author_sort Barrett, Hilary E.
collection PubMed
description PURPOSE: Atherosclerotic plaque development and progression signifies a complex inflammatory disease mediated by a multitude of proinflammatory leukocyte subsets. Using single photon emission computed tomography (SPECT) coupled with computed tomography (CT), this study tested a new dual-isotope acquisition protocol to assess each radiotracer’s capability to identify plaque phenotype and inflammation levels pertaining to leukocytes expressing leukocyte function-associated antigen-1 (LFA-1) and the leukocyte subset of proinflammatory macrophages expressing somatostatin receptor subtype-2 (SST(2)). Individual radiotracer uptake was quantified and the presence of corresponding immunohistological cell markers was assessed. METHODS: Human symptomatic carotid plaque segments were obtained from endarterectomy. Segments were incubated in dual-isotope radiotracers [(111)In]In-DOTA-butylamino-NorBIRT ([(111)In]In-Danbirt) and [(99m)Tc]Tc-[N(0–1)(4),Asp(0),Tyr(3)]-octreotate ([(99m)Tc]Tc-Demotate 2) before scanning with SPECT/CT. Plaque phenotype was classified as pathological intimal thickening, fibrous cap atheroma or fibrocalcific using histology sections based on distinct morphological characteristics. Plaque segments were subsequently immuno-stained with LFA-1 and SST(2) and quantified in terms of positive area fraction and compared against the corresponding SPECT images. RESULTS: Focal uptake of co-localising dual-radiotracers identified the heterogeneous distribution of inflamed regions in the plaques which co-localised with positive immuno-stained regions of LFA-1 and SST(2). [(111)In]In-Danbirt and [(99m)Tc]Tc-Demotate 2 uptake demonstrated a significant positive correlation (r = 0.651; p = 0.001). Fibrous cap atheroma plaque phenotype correlated with the highest [(111)In]In-Danbirt and [(99m)Tc]Tc-Demotate 2 uptake compared with fibrocalcific plaques and pathological intimal thickening phenotypes, in line with the immunohistological analyses. CONCLUSION: A dual-isotope acquisition protocol permits the imaging of multiple leukocyte subsets and the pro-inflammatory macrophages simultaneously in atherosclerotic plaque tissue. [(111)In]In-Danbirt may have added value for assessing the total inflammation levels in atherosclerotic plaques in addition to classifying plaque phenotype.
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spelling pubmed-75677262020-10-19 Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach Barrett, Hilary E. Meester, Eric J. van Gaalen, Kim van der Heiden, Kim Krenning, Boudewijn J. Beekman, Freek J. de Blois, Erik de Swart, Jan Verhagen, H J Maina, Theodosia Nock, Berthold A. Norenberg, Jeffrey P. de Jong, Marion Gijsen, Frank J. H. Bernsen, Monique R. Eur J Nucl Med Mol Imaging Original Article PURPOSE: Atherosclerotic plaque development and progression signifies a complex inflammatory disease mediated by a multitude of proinflammatory leukocyte subsets. Using single photon emission computed tomography (SPECT) coupled with computed tomography (CT), this study tested a new dual-isotope acquisition protocol to assess each radiotracer’s capability to identify plaque phenotype and inflammation levels pertaining to leukocytes expressing leukocyte function-associated antigen-1 (LFA-1) and the leukocyte subset of proinflammatory macrophages expressing somatostatin receptor subtype-2 (SST(2)). Individual radiotracer uptake was quantified and the presence of corresponding immunohistological cell markers was assessed. METHODS: Human symptomatic carotid plaque segments were obtained from endarterectomy. Segments were incubated in dual-isotope radiotracers [(111)In]In-DOTA-butylamino-NorBIRT ([(111)In]In-Danbirt) and [(99m)Tc]Tc-[N(0–1)(4),Asp(0),Tyr(3)]-octreotate ([(99m)Tc]Tc-Demotate 2) before scanning with SPECT/CT. Plaque phenotype was classified as pathological intimal thickening, fibrous cap atheroma or fibrocalcific using histology sections based on distinct morphological characteristics. Plaque segments were subsequently immuno-stained with LFA-1 and SST(2) and quantified in terms of positive area fraction and compared against the corresponding SPECT images. RESULTS: Focal uptake of co-localising dual-radiotracers identified the heterogeneous distribution of inflamed regions in the plaques which co-localised with positive immuno-stained regions of LFA-1 and SST(2). [(111)In]In-Danbirt and [(99m)Tc]Tc-Demotate 2 uptake demonstrated a significant positive correlation (r = 0.651; p = 0.001). Fibrous cap atheroma plaque phenotype correlated with the highest [(111)In]In-Danbirt and [(99m)Tc]Tc-Demotate 2 uptake compared with fibrocalcific plaques and pathological intimal thickening phenotypes, in line with the immunohistological analyses. CONCLUSION: A dual-isotope acquisition protocol permits the imaging of multiple leukocyte subsets and the pro-inflammatory macrophages simultaneously in atherosclerotic plaque tissue. [(111)In]In-Danbirt may have added value for assessing the total inflammation levels in atherosclerotic plaques in addition to classifying plaque phenotype. Springer Berlin Heidelberg 2020-04-15 2020 /pmc/articles/PMC7567726/ /pubmed/32291511 http://dx.doi.org/10.1007/s00259-020-04776-0 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Barrett, Hilary E.
Meester, Eric J.
van Gaalen, Kim
van der Heiden, Kim
Krenning, Boudewijn J.
Beekman, Freek J.
de Blois, Erik
de Swart, Jan
Verhagen, H J
Maina, Theodosia
Nock, Berthold A.
Norenberg, Jeffrey P.
de Jong, Marion
Gijsen, Frank J. H.
Bernsen, Monique R.
Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach
title Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach
title_full Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach
title_fullStr Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach
title_full_unstemmed Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach
title_short Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach
title_sort imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope spect approach
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567726/
https://www.ncbi.nlm.nih.gov/pubmed/32291511
http://dx.doi.org/10.1007/s00259-020-04776-0
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