title: A comparison of four PET tracers for brain hypoxia mapping in a rodent model of stroke.
abstract: BACKGROUND
  Severe brain hypoxia in the territory of the occluded artery is a key feature of ischemic stroke. This region can be imaged using positron emission tomography (PET) and the standard hypoxia radiotracer (18)F-fluoromisonidazole ((18)F-FMISO). However, the utility of (18)F-FMISO is limited by its slow accumulation in the lesion. Therefore, this study investigated three hypoxia-sensitive radiotracers, namely the nitroimidazole (18)F-fluoroazomycin arabinoside ((18)F-FAZA) and two (64)Cu bis(thiosemicarbazone) complexes ((64)Cu-ATSM and (64)Cu-ATSE), expected to have improved pharmacokinetic profiles relative to (18)F-FMISO, in a rodent model of ischemic stroke.
  
  
  METHODS
  In anaesthetised Wistar rats, the distal middle cerebral artery was permanently occluded by electrocoagulation, the radiotracers administered intravenously and animals PET scanned for up to 3hours, followed by T2-weighted magnetic resonance imaging to map the infarct.
  
  
  RESULTS
  As expected, late and prominent (18)F-FMISO retention was observed despite lower tracer delivery into the affected region. Time-activity curves revealed that both (64)Cu-ATSM and (64)Cu-ATSE showed rapid entry and efflux from the brain, but did not show significant accumulation in the lesion. (18)F-FAZA showed limited brain penetration, and accumulation in the lesion was inconsistent, low and as slow as (18)F-FMISO.
  
  
  CONCLUSIONS
  This study suggests further development of these radiotracers as hypoxia markers for ischemic stroke may not be warranted.
authors.affiliation: Department of Clinical Neurosciences, Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK. djw84@wbic.cam.ac.uk
authors.forename: David J
authors.initials: DJ
authors.lastname: Williamson
authors.forename: Sohail
authors.initials: S
authors.lastname: Ejaz
authors.forename: Sergey
authors.initials: S
authors.lastname: Sitnikov
authors.forename: Tim D
authors.initials: TD
authors.lastname: Fryer
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sawiak
authors.forename: Paul
authors.initials: P
authors.lastname: Burke
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Baron
authors.forename: Franklin I
authors.initials: FI
authors.lastname: Aigbirhio
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology*; D015687:Cell Hypoxia; D004195:Disease Models, Animal; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000000981:diagnostic imaging* / Q000473:pathology*
chemical_list: D011849:Radioactive Tracers; D019275:Radiopharmaceuticals