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Molecular Imaging of Inflammation in a Mouse Model of Atherosclerosis Using a Zirconium-89-Labeled Probe

BACKGROUND: Beyond clinical atherosclerosis imaging of vessel stenosis and plaque morphology, early detection of inflamed atherosclerotic lesions by molecular imaging could improve risk assessment and clinical management in high-risk patients. To identify inflamed atherosclerotic lesions by molecula...

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Autores principales: Ahmed, Mona, Tegnebratt, Tetyana, Tran, Thuy A, Lu, Li, Damberg, Peter, Gisterå, Anton, Tarnawski, Laura, Bone, Dianna, Hedin, Ulf, Eriksson, Per, Holmin, Staffan, Gustafsson, Björn, Caidahl, Kenneth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434576/
https://www.ncbi.nlm.nih.gov/pubmed/32884268
http://dx.doi.org/10.2147/IJN.S256395
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author Ahmed, Mona
Tegnebratt, Tetyana
Tran, Thuy A
Lu, Li
Damberg, Peter
Gisterå, Anton
Tarnawski, Laura
Bone, Dianna
Hedin, Ulf
Eriksson, Per
Holmin, Staffan
Gustafsson, Björn
Caidahl, Kenneth
author_facet Ahmed, Mona
Tegnebratt, Tetyana
Tran, Thuy A
Lu, Li
Damberg, Peter
Gisterå, Anton
Tarnawski, Laura
Bone, Dianna
Hedin, Ulf
Eriksson, Per
Holmin, Staffan
Gustafsson, Björn
Caidahl, Kenneth
author_sort Ahmed, Mona
collection PubMed
description BACKGROUND: Beyond clinical atherosclerosis imaging of vessel stenosis and plaque morphology, early detection of inflamed atherosclerotic lesions by molecular imaging could improve risk assessment and clinical management in high-risk patients. To identify inflamed atherosclerotic lesions by molecular imaging in vivo, we studied the specificity of our radiotracer based on maleylated (Mal) human serum albumin (HSA), which targets key features of unstable atherosclerotic lesions. MATERIALS AND METHODS: Mal-HSA was radiolabeled with a positron-emitting metal ion, zirconium-89 ((89)Zr(4+)). The targeting potential of this probe was compared with unspecific (89)Zr-HSA and (18)F-FDG in an experimental model of atherosclerosis (Apoe(–/–) mice, n=22), and compared with wild-type (WT) mice (C57BL/6J, n=21) as controls. RESULTS: PET/MRI, gamma counter measurements, and autoradiography showed the accumulation of (89)Zr-Mal-HSA in the atherosclerotic lesions of Apoe(–/–) mice. The maximum standardized uptake values (SUV(max)) for (89)Zr-Mal-HSA at 16 and 20 weeks were 26% and 20% higher (P<0.05) in Apoe(–/–) mice than in control WT mice, whereas no difference in SUV(max) was observed for (18)F-FDG in the same animals. (89)Zr-Mal-HSA uptake in the aorta, as evaluated by a gamma counter 48 h postinjection, was 32% higher (P<0.01) for Apoe(–/–) mice than in WT mice, and the aorta-to-blood ratio was 8-fold higher (P<0.001) for (89)Zr-Mal-HSA compared with unspecific (89)Zr-HSA. HSA-based probes were mainly distributed to the liver, spleen, kidneys, bone, and lymph nodes. The phosphor imaging autoradiography (PI-ARG) results corroborated the PET and gamma counter measurements, showing higher accumulation of (89)Zr-Mal-HSA in the aortas of Apoe(–/–) mice than in WT mice (9.4±1.4 vs 0.8±0.3%; P<0.001). CONCLUSION: (89)Zr radiolabeling of Mal-HSA probes resulted in detectable activity in atherosclerotic lesions in aortas of Apoe(–/–) mice, as demonstrated by quantitative in vivo PET/MRI. (89)Zr-Mal-HSA appears to be a promising diagnostic tool for the early identification of macrophage-rich areas of inflammation in atherosclerosis.
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spelling pubmed-74345762020-09-02 Molecular Imaging of Inflammation in a Mouse Model of Atherosclerosis Using a Zirconium-89-Labeled Probe Ahmed, Mona Tegnebratt, Tetyana Tran, Thuy A Lu, Li Damberg, Peter Gisterå, Anton Tarnawski, Laura Bone, Dianna Hedin, Ulf Eriksson, Per Holmin, Staffan Gustafsson, Björn Caidahl, Kenneth Int J Nanomedicine Original Research BACKGROUND: Beyond clinical atherosclerosis imaging of vessel stenosis and plaque morphology, early detection of inflamed atherosclerotic lesions by molecular imaging could improve risk assessment and clinical management in high-risk patients. To identify inflamed atherosclerotic lesions by molecular imaging in vivo, we studied the specificity of our radiotracer based on maleylated (Mal) human serum albumin (HSA), which targets key features of unstable atherosclerotic lesions. MATERIALS AND METHODS: Mal-HSA was radiolabeled with a positron-emitting metal ion, zirconium-89 ((89)Zr(4+)). The targeting potential of this probe was compared with unspecific (89)Zr-HSA and (18)F-FDG in an experimental model of atherosclerosis (Apoe(–/–) mice, n=22), and compared with wild-type (WT) mice (C57BL/6J, n=21) as controls. RESULTS: PET/MRI, gamma counter measurements, and autoradiography showed the accumulation of (89)Zr-Mal-HSA in the atherosclerotic lesions of Apoe(–/–) mice. The maximum standardized uptake values (SUV(max)) for (89)Zr-Mal-HSA at 16 and 20 weeks were 26% and 20% higher (P<0.05) in Apoe(–/–) mice than in control WT mice, whereas no difference in SUV(max) was observed for (18)F-FDG in the same animals. (89)Zr-Mal-HSA uptake in the aorta, as evaluated by a gamma counter 48 h postinjection, was 32% higher (P<0.01) for Apoe(–/–) mice than in WT mice, and the aorta-to-blood ratio was 8-fold higher (P<0.001) for (89)Zr-Mal-HSA compared with unspecific (89)Zr-HSA. HSA-based probes were mainly distributed to the liver, spleen, kidneys, bone, and lymph nodes. The phosphor imaging autoradiography (PI-ARG) results corroborated the PET and gamma counter measurements, showing higher accumulation of (89)Zr-Mal-HSA in the aortas of Apoe(–/–) mice than in WT mice (9.4±1.4 vs 0.8±0.3%; P<0.001). CONCLUSION: (89)Zr radiolabeling of Mal-HSA probes resulted in detectable activity in atherosclerotic lesions in aortas of Apoe(–/–) mice, as demonstrated by quantitative in vivo PET/MRI. (89)Zr-Mal-HSA appears to be a promising diagnostic tool for the early identification of macrophage-rich areas of inflammation in atherosclerosis. Dove 2020-08-14 /pmc/articles/PMC7434576/ /pubmed/32884268 http://dx.doi.org/10.2147/IJN.S256395 Text en © 2020 Ahmed et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Ahmed, Mona
Tegnebratt, Tetyana
Tran, Thuy A
Lu, Li
Damberg, Peter
Gisterå, Anton
Tarnawski, Laura
Bone, Dianna
Hedin, Ulf
Eriksson, Per
Holmin, Staffan
Gustafsson, Björn
Caidahl, Kenneth
Molecular Imaging of Inflammation in a Mouse Model of Atherosclerosis Using a Zirconium-89-Labeled Probe
title Molecular Imaging of Inflammation in a Mouse Model of Atherosclerosis Using a Zirconium-89-Labeled Probe
title_full Molecular Imaging of Inflammation in a Mouse Model of Atherosclerosis Using a Zirconium-89-Labeled Probe
title_fullStr Molecular Imaging of Inflammation in a Mouse Model of Atherosclerosis Using a Zirconium-89-Labeled Probe
title_full_unstemmed Molecular Imaging of Inflammation in a Mouse Model of Atherosclerosis Using a Zirconium-89-Labeled Probe
title_short Molecular Imaging of Inflammation in a Mouse Model of Atherosclerosis Using a Zirconium-89-Labeled Probe
title_sort molecular imaging of inflammation in a mouse model of atherosclerosis using a zirconium-89-labeled probe
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434576/
https://www.ncbi.nlm.nih.gov/pubmed/32884268
http://dx.doi.org/10.2147/IJN.S256395
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