title: Fluorescence labeled microbubbles for multimodal imaging.
abstract: Air-filled polyvinyl alcohol microbubbles (PVA-MBs) were recently introduced as a contrast agent for ultrasound imaging. In the present study, we explore the possibility of extending their application in multimodal imaging by labeling them with a near infrared (NIR) fluorophore, VivoTag-680. PVA-MBs were injected intravenously into FVB/N female mice and their dynamic biodistribution over 24 h was determined by 3D-fluorescence imaging co-registered with 3D-μCT imaging, to verify the anatomic location. To further confirm the biodistribution results from in vivo imaging, organs were removed and examined histologically using bright field and fluorescence microscopy. Fluorescence imaging detected PVA-MB accumulation in the lungs within the first 30 min post-injection. Redistribution to a low extent was observed in liver and kidneys at 4 h, and to a high extent mainly in the liver and spleen at 24 h. Histology confirmed PVA-MB localization in lung capillaries and macrophages. In the liver, they were associated with Kupffer cells; in the spleen, they were located mostly within the marginal-zone. Occasional MBs were observed in the kidney glomeruli and interstitium. The potential application of PVA-MBs as a contrast agent was also studied using ultrasound (US) imaging in subcutaneous and orthotopic pancreatic cancer mouse models, to visualize blood flow within the tumor mass. In conclusion, this study showed that PVA-MBs are useful as a contrast agent for multimodal imaging.
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet (KI), Stockholm, Sweden; Experimental Cancer Medicine (ECM), Department of Laboratory Medicine, KI, Sweden. Electronic address: asa.barrefelt@ki.se.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Barrefelt
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet (KI), Stockholm, Sweden. Electronic address: ying.zhao.1@ki.se.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Medical Engineering, School of Technology and Health, Royal Institute of Technology (KTH), Stockholm, Sweden. Electronic address: malinl@sth.kth.se.
authors.forename: Malin K
authors.initials: MK
authors.lastname: Larsson
authors.affiliation: Surflay Nanotec GmbH, 12489 Berlin, Germany. Electronic address: g.egri@surflay.com.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Egri
authors.affiliation: Karolinska Institute Core Facility for Morphologic Phenotype Analysis, Karolinska University Hospital-Huddinge, Stockholm, Sweden. Electronic address: Raoul.Kuiper@ki.se.
authors.forename: Raoul V
authors.initials: RV
authors.lastname: Kuiper
authors.affiliation: PerkinElmer, 68 Elm St., Hopkinton, MA 01748, USA. Electronic address: Jorg.Hamm@perkinelmer.com.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamm
authors.affiliation: Experimental Cancer Medicine (ECM), Department of Laboratory Medicine, KI, Sweden. Electronic address: maryam.saghafian@ki.se.
authors.forename: Maryam
authors.initials: M
authors.lastname: Saghafian
authors.affiliation: Department of Molecular Medicine and Surgery, KI, Dept. Clin Phys, Karolinska University Hospital, Stockholm, Sweden. Electronic address: Kenneth.Caidahl@ki.se.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Caidahl
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet (KI), Stockholm, Sweden. Electronic address: torkel.brismar@karolinska.se.
authors.forename: Torkel B
authors.initials: TB
authors.lastname: Brismar
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet (KI), Stockholm, Sweden. Electronic address: Peter.Aspelin@ki.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Aspelin
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet (KI), Stockholm, Sweden. Electronic address: rainer.heuchel@ki.se.
authors.forename: Rainer
authors.initials: R
authors.lastname: Heuchel
authors.affiliation: Department of Materials and Nano Physics, Division of Functional Materials (FNM), Royal Institute of Technology (KTH), Stockholm, Sweden. Electronic address: mamoun@kth.se.
authors.forename: Mamoun
authors.initials: M
authors.lastname: Muhammed
authors.affiliation: Surflay Nanotec GmbH, 12489 Berlin, Germany. Electronic address: l.daehne@surflay.com.
authors.forename: Lars
authors.initials: L
authors.lastname: Dähne
authors.affiliation: Experimental Cancer Medicine (ECM), Department of Laboratory Medicine, KI, Sweden; Clinical Research Center (KFC, Novum), Karolinska University Hospital-Huddinge, Stockholm, Sweden. Electronic address: Moustapha.hassan@ki.se.
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hassan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D005260:Female; D005456:Fluorescent Dyes; D064593:Heterografts; D006801:Humans; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D064847:Multimodal Imaging / Q000379:methods*; D061848:Optical Imaging; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging; D014463:Ultrasonography; D055114:X-Ray Microtomography
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes
keywords: Fluorescence; In vivo imaging systems; Micro-computed tomography; Micro-ultrasound; Microbubbles; Near infrared (NIR); VivoTag 680