Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat

Åsa Barrefelt,1,2,* Maryam Saghafian,2,* Raoul Kuiper,3 Fei Ye,4 Gabriella Egri,5 Moritz Klickermann,5 Torkel B Brismar,1 Peter Aspelin,1 Mamoun Muhammed,4 Lars Dähne,5 Moustapha Hassan2,6 1Department of Clinical Science, Intervention and Technology, Division of Medical Imaging an...

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Autores principales:	Barrefelt A, Saghafian M, Kuiper R, Ye F, Egri G, Klickermann M, Brismar TB, Aspelin P, Muhammed M, D&auml;hne L, Hassan M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0a02a94d6163497799c7fc6ece050f7b
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spelling	oai:doaj.org-article:0a02a94d6163497799c7fc6ece050f7b2021-12-02T05:10:26ZBiodistribution, kinetics, and biological fate of SPION microbubbles in the rat1176-91141178-2013https://doaj.org/article/0a02a94d6163497799c7fc6ece050f7b2013-08-01T00:00:00Zhttp://www.dovepress.com/biodistribution-kinetics-and-biological-fate-of-spion-microbubbles-in--a14153https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Åsa Barrefelt,1,2,* Maryam Saghafian,2,* Raoul Kuiper,3 Fei Ye,4 Gabriella Egri,5 Moritz Klickermann,5 Torkel B Brismar,1 Peter Aspelin,1 Mamoun Muhammed,4 Lars Dähne,5 Moustapha Hassan2,6 1Department of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, and Department of Radiology, Karolinska University Hospital-Huddinge, Stockholm, Sweden; 2Experimental Cancer Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; 3Karolinska Institute Core Facility for Morphologic Phenotype Analysis, Clinical Research Center, Karolinska University Hospital-Huddinge, Stockholm, Sweden; 4Division of Functional Materials, Department of Materials and Nano Physics, Royal Institute of Technology, Stockholm, Sweden; 5Surflay Nanotec GmbH, Berlin, Germany; 6Clinical Research Center, Karolinska University Hospital-Huddinge, Stockholm, Sweden *These authors contributed equally to this work Background: In the present investigation, we studied the kinetics and biodistribution of a contrast agent consisting of poly(vinyl alcohol) (PVA) microbubbles containing superparamagnetic iron oxide (SPION) trapped between the PVA layers (SPION microbubbles). Methods: The biological fate of SPION microbubbles was determined in Sprague-Dawley rats after intravenous administration. Biodistribution and elimination of the microbubbles were studied in rats using magnetic resonance imaging for a period of 6 weeks. The rats were sacrificed and perfusion-fixated at different time points. The magnetic resonance imaging results obtained were compared with histopathologic findings in different organs. Results: SPION microbubbles could be detected in the liver using magnetic resonance imaging as early as 10 minutes post injection. The maximum signal was detected between 24 hours and one week post injection. Histopathology showed the presence of clustered SPION microbubbles predominantly in the lungs from the first time point investigated (10 minutes). The frequency of microbubbles declined in the pulmonary vasculature and increased in pulmonary, hepatic, and splenic macrophages over time, resulting in a relative shift from the lungs to the spleen and liver. Meanwhile, macrophages showed increasing signs of cytoplasmic iron accumulation, initially in the lungs, then followed by other organs. Conclusion: The present investigation highlights the biological behavior of SPION microbubbles, including organ distribution over time and indications for biodegradation. The present results are essential for developing SPION microbubbles as a potential contrast agent and/or a drug delivery vehicle for specific organs. Such a vehicle will facilitate the use of multimodality imaging techniques, including ultrasound, magnetic resonance imaging, and single positron emission computed tomography, and hence improve diagnostics, therapy, and the ability to monitor the efficacy of treatment. Keywords: biodistribution, microbubbles, superparamagnetic iron oxide, pharmacokinetics, magnetic resonance imaging, histopathologyBarrefelt ASaghafian MKuiper RYe FEgri GKlickermann MBrismar TBAspelin PMuhammed MD&auml;hne LHassan MDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 3241-3254 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Barrefelt A Saghafian M Kuiper R Ye F Egri G Klickermann M Brismar TB Aspelin P Muhammed M D&auml;hne L Hassan M Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat
description	Åsa Barrefelt,1,2,* Maryam Saghafian,2,* Raoul Kuiper,3 Fei Ye,4 Gabriella Egri,5 Moritz Klickermann,5 Torkel B Brismar,1 Peter Aspelin,1 Mamoun Muhammed,4 Lars Dähne,5 Moustapha Hassan2,6 1Department of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, and Department of Radiology, Karolinska University Hospital-Huddinge, Stockholm, Sweden; 2Experimental Cancer Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; 3Karolinska Institute Core Facility for Morphologic Phenotype Analysis, Clinical Research Center, Karolinska University Hospital-Huddinge, Stockholm, Sweden; 4Division of Functional Materials, Department of Materials and Nano Physics, Royal Institute of Technology, Stockholm, Sweden; 5Surflay Nanotec GmbH, Berlin, Germany; 6Clinical Research Center, Karolinska University Hospital-Huddinge, Stockholm, Sweden *These authors contributed equally to this work Background: In the present investigation, we studied the kinetics and biodistribution of a contrast agent consisting of poly(vinyl alcohol) (PVA) microbubbles containing superparamagnetic iron oxide (SPION) trapped between the PVA layers (SPION microbubbles). Methods: The biological fate of SPION microbubbles was determined in Sprague-Dawley rats after intravenous administration. Biodistribution and elimination of the microbubbles were studied in rats using magnetic resonance imaging for a period of 6 weeks. The rats were sacrificed and perfusion-fixated at different time points. The magnetic resonance imaging results obtained were compared with histopathologic findings in different organs. Results: SPION microbubbles could be detected in the liver using magnetic resonance imaging as early as 10 minutes post injection. The maximum signal was detected between 24 hours and one week post injection. Histopathology showed the presence of clustered SPION microbubbles predominantly in the lungs from the first time point investigated (10 minutes). The frequency of microbubbles declined in the pulmonary vasculature and increased in pulmonary, hepatic, and splenic macrophages over time, resulting in a relative shift from the lungs to the spleen and liver. Meanwhile, macrophages showed increasing signs of cytoplasmic iron accumulation, initially in the lungs, then followed by other organs. Conclusion: The present investigation highlights the biological behavior of SPION microbubbles, including organ distribution over time and indications for biodegradation. The present results are essential for developing SPION microbubbles as a potential contrast agent and/or a drug delivery vehicle for specific organs. Such a vehicle will facilitate the use of multimodality imaging techniques, including ultrasound, magnetic resonance imaging, and single positron emission computed tomography, and hence improve diagnostics, therapy, and the ability to monitor the efficacy of treatment. Keywords: biodistribution, microbubbles, superparamagnetic iron oxide, pharmacokinetics, magnetic resonance imaging, histopathology
format	article
author	Barrefelt A Saghafian M Kuiper R Ye F Egri G Klickermann M Brismar TB Aspelin P Muhammed M D&auml;hne L Hassan M
author_facet	Barrefelt A Saghafian M Kuiper R Ye F Egri G Klickermann M Brismar TB Aspelin P Muhammed M D&auml;hne L Hassan M
author_sort	Barrefelt A
title	Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat
title_short	Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat
title_full	Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat
title_fullStr	Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat
title_full_unstemmed	Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat
title_sort	biodistribution, kinetics, and biological fate of spion microbubbles in the rat
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/0a02a94d6163497799c7fc6ece050f7b
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Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat

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