title: Validation of fluorescence molecular tomography/micro-CT multimodal imaging in vivo in rats.
abstract: OBJECTIVE
  Rats are important preclinical models for studying breast cancer metastasis and bone pathologies. In these research areas, fluorescence molecular tomography (FMT) is commonly applied for quantitative three-dimensional (3D) imaging in mice. However, uncertainties due to strong depth dependency of FMT signal and spatial resolution require a validation study in rats.
  
  
  METHODS
  FMT performance in rats was assessed based on co-registered FMT/micro-computed tomography (micro-CT) reconstructed volumes obtained from optical phantoms and from models relevant for tumor imaging, bone remodeling and biodistribution analysis of nanoparticles.
  
  
  RESULTS
  FMT reconstructions within 20-mm-thick optical phantoms were accurate (95 ± 11 % recovery), precise (CV ≤ 8 %) and linear (R(2) > 0.9788) over a range of 78-2,500 nM of the near infrared fluorescent agent VivoTag 750 (VT(750)). In vivo, implanted defined fluorescent targets yielded a recovery of 105 ± 5 % and successfully co-registered with micro-CT delineated structures. Additionally, using the bone-targeting imaging agent Osteosense 750, regions of neo bone formation identified by FMT could be mapped to the region of epiphyseal growth plates observed in micro-CT images. Finally, as a proof of concept, to monitor nanoparticulate drug pharmacokinetics in rat subjects the accumulation/clearance of VT(750)-albumin conjugate in/from the liver was followed at 11 different time points over a period of 2 weeks by FMT/micro-CT.
  
  
  CONCLUSIONS
  FMT imaging has been validated in optical phantoms as well as in 160 g rats, and sequential FMT/micro-CT imaging can be considered as a useful tool for preclinical research in rats.
authors.affiliation: Institute for Macromolecular Chemistry, University of Freiburg, 79104, Freiburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vonwil
authors.forename: Jon
authors.initials: J
authors.lastname: Christensen
authors.forename: Sascha
authors.initials: S
authors.lastname: Fischer
authors.forename: Olaf
authors.initials: O
authors.lastname: Ronneberger
authors.forename: V Prasad
authors.initials: VP
authors.lastname: Shastri
mesh_terms: D000818:Animals; D005453:Fluorescence; D064847:Multimodal Imaging; D051381:Rats; D017208:Rats, Wistar; D055114:X-Ray Microtomography / Q000379:methods*