title: Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, and Department of Radiology, Karolinska University Hospital-Huddinge, Stockholm, Sweden ; Experimental Cancer Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Barrefelt
authors.forename: Maryam
authors.initials: M
authors.lastname: Saghafian
authors.forename: Raoul
authors.initials: R
authors.lastname: Kuiper
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Gabriella
authors.initials: G
authors.lastname: Egri
authors.forename: Moritz
authors.initials: M
authors.lastname: Klickermann
authors.forename: Torkel B
authors.initials: TB
authors.lastname: Brismar
authors.forename: Peter
authors.initials: P
authors.lastname: Aspelin
authors.forename: Mamoun
authors.initials: M
authors.lastname: Muhammed
authors.forename: Lars
authors.initials: L
authors.lastname: Dähne
authors.forename: Moustapha
authors.initials: M
authors.lastname: Hassan
mesh_terms: D000818:Animals; D002214:Capsules / Q000737:chemistry* / Q000493:pharmacokinetics*; D003287:Contrast Media / Q000737:chemistry / Q000493:pharmacokinetics; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity / Q000502:physiology; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D051598:Whole Body Imaging / Q000379:methods*
chemical_list: D002214:Capsules; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10; D011142:Polyvinyl Alcohol
keywords: biodistribution; histopathology; magnetic resonance imaging; microbubbles; pharmacokinetics; superparamagnetic iron oxide
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