title: Metabolic pathway and distribution of superparamagnetic iron oxide nanoparticles: in vivo study.
abstract: BACKGROUND
  Experimental tissue fusion benefits from the selective heating of superparamagnetic iron oxide nanoparticles (SPIONs) under high frequency irradiation. However, the metabolic pathways of SPIONs for tissue fusion remain unknown. Hence, the goal of this in vivo study was to analyze the distribution of SPIONs in different organs by means of magnetic resonance imaging (MRI) and histological analysis after a SPION-containing patch implantation.
  
  
  METHODS
  SPION-containing patches were implanted in rats. Three animal groups were studied histologically over six months. Degradation assessment of the SPION-albumin patch was performed in vivo using MRI for iron content localization and biodistribution.
  
  
  RESULTS
  No SPION degradation or accumulation into the reticuloendothelial system was detected by MRI, MRI relaxometry, or histology, outside the area of the implantation patch. Concentrations from 0.01 μg/mL to 25 μg/mL were found to be hyperintense in T1-like gradient echo sequences. The best differentiation of concentrations was found in T2 relaxometry, susceptibility-sensitive gradient echo sequences, and in high repetition time T2 images. Qualitative and semiquantitative visualization of small concentrations and accumulation of SPIONs by MRI are feasible. In histological liver samples, Kupffer cells were significantly correlated with postimplantation time, but no differences were observed between sham-treated and induction/no induction groups. Transmission electron microscopy showed local uptake of SPIONs in macrophages and cells of the reticuloendothelial system. Apoptosis staining using caspase showed no increased toxicity compared with sham-treated tissue. Implanted SPION patches were relatively inert with slow, progressive local degradation over the six-month period. No distant structural alterations in the studied tissue could be observed.
  
  
  CONCLUSIONS
  Systemic bioavailability may play a role in specific SPION implant toxicity and therefore the local degradation process is a further aspect to be assessed in future studies.
authors: Department of Neurosurgery, InselspitalBern, 3010 Berne, Switzerland.
authors: Eva K
authors: EK
authors: Schlachter
authors: Hans Ruedi
authors: HR
authors: Widmer
authors: Amadé
authors: A
authors: Bregy
authors: Tarja
authors: T
authors: Lönnfors-Weitzel
authors: Istvan
authors: I
authors: Vajtai
authors: Nadia
authors: N
authors: Corazza
authors: Vianney J P
authors: VJ
authors: Bernau
authors: Thilo
authors: T
authors: Weitzel
authors: Pasquale
authors: P
authors: Mordasini
authors: Johannes
authors: J
authors: Slotboom
authors: Gudrun
authors: G
authors: Herrmann
authors: Serge
authors: S
authors: Bogni
authors: Heinrich
authors: H
authors: Hofmann
authors: Martin
authors: M
authors: Frenz
authors: Michael
authors: M
authors: Reinert
mesh_terms: D000818:Animals; D005290:Ferric Compounds / Q000378:metabolism / Q000493:pharmacokinetics*; D006651:Histocytochemistry; D020007:Implants, Experimental; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide