title: Regional particle size dependent deposition of inhaled aerosols in rats and mice.
abstract: BACKGROUND
  The current data analysis tools in nuclear medicine have not been used to evaluate intra organ regional deposition patterns of pharmaceutical aerosols in preclinical species.
  
  
  OBJECTIVE
  This study evaluates aerosol deposition patterns as a function of particle size in rats and mice using novel image analysis techniques.
  
  
  METHODS
  Mice and rats were exposed to radiolabeled polydisperse aerosols at 0.5, 1.0, 3.0, and 5.0 µm MMAD followed by SPECT/CT imaging for deposition analysis. Images were quantified for both macro deposition patterns and regional deposition analysis using the LRRI-developed Onion Model.
  
  
  RESULTS
  The deposition fraction in both rats and mice was shown to increase as the particle size decreased, with greater lung deposition in rats at all particle sizes. The Onion Model indicated that the smaller particle sizes resulted in increased peripheral deposition.
  
  
  CONCLUSIONS
  These data contrast the commonly used 10% deposition fraction for all aerosols between 1.0 and 5.0 µm and indicate that lung deposition fraction in this range does change with particle size. When compared to historical data, the 1.0, 3.0, and 5.0 µm particles result in similar lung deposition fractions; however, the 0.5 µm lung deposition fraction is markedly different. This is probably caused by the current aerosols that were polydisperse to reflect current pharmaceutical aerosols, while the historical data were generated with monodisperse aerosols.
  
  
  CONCLUSIONS
  The deposition patterns of aerosols between 0.5 and 5.0 µm showed an increase in both overall and peripheral deposition as the particle size decreased. The Onion Model allows a more complex analysis of regional deposition in preclinical models.
authors.affiliation: Lovelace Respiratory Research Institute , Albuquerque, NM 87108, USA. pkuehl@lrri.org
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kuehl
authors.forename: Tamara L
authors.initials: TL
authors.lastname: Anderson
authors.forename: Gabriel
authors.initials: G
authors.lastname: Candelaria
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gershman
authors.forename: Ky
authors.initials: K
authors.lastname: Harlin
authors.forename: Jacob Y
authors.initials: JY
authors.lastname: Hesterman
authors.forename: Thomas
authors.initials: T
authors.lastname: Holmes
authors.forename: John
authors.initials: J
authors.lastname: Hoppin
authors.forename: Christian
authors.initials: C
authors.lastname: Lackas
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Norenberg
authors.forename: Hongang
authors.initials: H
authors.lastname: Yu
authors.forename: Jacob D
authors.initials: JD
authors.lastname: McDonald
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D064847:Multimodal Imaging; D010316:Particle Size; D052638:Particulate Matter / Q000008:administration & dosage / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D051381:Rats; D011916:Rats, Inbred F344; D013667:Technetium; D014057:Tomography, X-Ray Computed
chemical_list: D000336:Aerosols; D052638:Particulate Matter; D013667:Technetium