title: Fluorescent bacterial magnetic nanoparticles as bimodal contrast agents.
abstract: OBJECTIVE
  The purpose of this study was to assess whether fluorochrome-coupled bacterial magnetic nanoparticles can be used as bimodal contrast agent for both magnetic resonance imaging (MRI) and near-infrared fluorescence optical (NIRF) imaging of cultured macrophages.
  
  
  METHODS
  Bacterial magnetic nanoparticles (magnetosomes, particle diameter: 42 nm) were harvested from Magnetospirillum gryphiswaldense and characterized by using MRI. After covalent coupling to the fluorescent dye DY-676 (lambdaabs./lambdaem.= 676 nm/701 nm, Dyomics, Jena, Germany), the fluorescent magnetosomes were analyzed by fluorescence-activated cell sorting. Subsequently, murine macrophages J774 were incubated with the bimodal contrast agent (3 hours) and examined by a whole-body near infrared small animal imaging system as well as by using a 1.5 T clinical MR system. Moreover, labeled cells were characterized using confocal laser scanning microscopy (CLSM) and ultrathin section transmission electron microscopy.
  
  
  RESULTS
  Characterization of the nanoparticles by MRI revealed R1 and R2 relaxivities of 3.2 mMs and 526 mMs, respectively. Fluorochrome-coupled magnetosomes exhibited increased fluorescence intensities at wavelengths >670 nm. Macrophages that were incubated with the contrast agent showed a significant fluorescence emission in the near infrared range as imaged with a whole body NIR imaging system, FACS analysis and CLSM. Moreover, CLSM data showed the greatest fluorescence intensities within intracellular compartments and colocalized with the magnetosomes. With MRI, both T1 and T2 relaxation times were substantially shortened at concentrations greater than 600 cells/microL.
  
  
  CONCLUSIONS
  Macrophages could be labeled with fluorescent magnetosomes, and they were successfully imaged using both a 1.5 T MR scanner as well as with NIRF optical methods. The use of this bimodal contrast agent for diagnostic purposes may benefit from the excellent spatial resolution of the MRI and the high sensitivity of the fluorescence imaging.
authors.affiliation: Institute for Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, Jena, Germany. marcus.lisy@med.uni-jena.de
authors.forename: Marcus-René
authors.initials: MR
authors.lastname: Lisy
authors.forename: Annegret
authors.initials: A
authors.lastname: Hartung
authors.forename: Claus
authors.initials: C
authors.lastname: Lang
authors.forename: Dirk
authors.initials: D
authors.lastname: Schüler
authors.forename: Walter
authors.initials: W
authors.lastname: Richter
authors.forename: Jürgen R
authors.initials: JR
authors.lastname: Reichenbach
authors.forename: Werner A
authors.initials: WA
authors.lastname: Kaiser
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hilger
mesh_terms: D018929:Cell Culture Techniques; D003287:Contrast Media; D005240:Feasibility Studies; D005453:Fluorescence; D006801:Humans; D008264:Macrophages; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D053758:Nanoparticles
chemical_list: D003287:Contrast Media