title: Imaging the ischemic penumbra with 18F-fluoromisonidazole in a rat model of ischemic stroke.
abstract: OBJECTIVE
  The ischemic penumbra is a major focus of stroke research. 18F-fluoromisonidazole (18F-FMISO), a positron emission tomography (PET) marker of hypoxic cells, has shown promise as a technique to image the penumbra in humans. Our aim was to delineate the pattern of 18F-FMISO binding in a rat middle cerebral artery transient thread-occlusion model, and correlate this with tissue outcome at 24 hours. We hypothesized that the pattern of 18F-FMISO binding would mimic that seen in humans.
  
  
  METHODS
  Thirty-eight rats underwent 2 hours transient middle cerebral artery (MCA) occlusion, and then received 18F-FMISO at time points from 0.5 to 22 hours post-MCA occlusion and were killed 2 hours later. Autoradiographic assessment of 18F-FMISO binding and assessment (triphenyltetrazolium chloride) of the area of infarction were performed on tissue slices.
  
  
  RESULTS
  Until 1 hour after MCA occlusion, 18F-FMISO binding was increased in the entire MCA territory, with little or no infarction visible. Over the next 5 hours, the pattern of binding evolved to a small rim of intensely binding tissue surrounding the infarct core, which itself showed reduced binding compared with the contralateral hemisphere. By 24 hours, there was minimal accumulation of 18F-FMISO binding and a large area of infarction.
  
  
  CONCLUSIONS
  The pattern of 18F-FMISO binding rats reproduced the pattern seen in humans, consistent with this tracer being a marker of the ischemic penumbra in both species. This technique may have application in studying the ischemic penumbra in animal models, and correlating this with similar studies in humans.
authors.affiliation: Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Saita
authors.forename: Michelle
authors.initials: M
authors.lastname: Chen
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Spratt
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Porritt
authors.forename: Gabriel T
authors.initials: GT
authors.lastname: Liberatore
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Read
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Levi
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.forename: Uwe
authors.initials: U
authors.lastname: Ackermann
authors.forename: Henri J
authors.initials: HJ
authors.lastname: Tochon-Danguy
authors.forename: John I
authors.initials: JI
authors.lastname: Sachinidis
authors.forename: David W
authors.initials: DW
authors.lastname: Howells
mesh_terms: D000818:Animals; D001345:Autoradiography; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging* / Q000473:pathology; D008297:Male; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000000981:diagnostic imaging* / Q000473:pathology; D014055:Tomography, Emission-Computed
chemical_list: C031843:fluoromisonidazole; D008920:Misonidazole