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Investigation of the elimination process of a multimodal polymer-shelled contrast agent in rats using ultrasound and transmission electron microscopy

Article type: Research Article

Authors: Härmark, Johan; | Larsson, Malin K. | Razuvajev, Anton | Koeck, Philip J.B. | Paradossi, Gaio | Brodin, Lars-Åke | Caidahl, Kenneth | Hebert, Hans | Bjällmark, Anna;

Affiliations: School of Technology and Health, KTH Royal Institute of Technology and Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden | Department of Medical Engineering, School of Technology of Health, KTH Royal Institute of Technology, Stockholm, Sweden | Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden | Department of Chemical Sciences and Technologies, Università di Roma Tor Vergata, Rome, Italy

Note: [] Corresponding author: Johan Härmark, School of Technology and Health, KTH Royal Institute of Technology, Alfred Nobels Allé 10, 141 52 Huddinge, Sweden. Tel.: +46 8 524 810 91; Fax: +46 8 21 83 68; E-mail: jharmark@kth.se

Keywords: Contrast agent, polymer, subcellular localization, transmission electron microscope, ultrasound imaging

DOI: 10.3233/BSI-140099

Journal: Biomedical Spectroscopy and Imaging, vol. 4, no. 1, pp. 81-93, 2015

Published: 2015
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Abstract

BACKGROUND: A novel polymer-shelled contrast agent (CA) with multimodal imaging and target specific potential was developed recently and tested for its acoustical properties using different in-vitro setups.

OBJECTIVE: The aim of this study was to investigate the elimination of three types of the novel polymer-shelled CA, one unmodified and two shell modified versions, in rats.

METHODS: The blood elimination time was estimated by measuring the image intensity, from ultrasound images of the common carotid artery, over time after a bolus injection of the three types of the novel CA. The commercially available CA SonoVue was used as a reference. The subcellular localization of the three CAs was investigated using transmission electron microscopy.

RESULTS: The ultrasound measurements indicated a blood half-life of 17–85 s for the different types of the novel CA, which was significant longer than the blood half-life time for SonoVue. Additionally, CAs were exclusively found in the circulatory system, either taken up by, or found in the vicinity of macrophages.

CONCLUSIONS: Compared to the commercially available CA SonoVue, the blood circulation times for the three types of the novel polymer-shelled CA were prolonged. Moreover, macrophages were suggested to be responsible for the elimination of the CA.

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