A comparison of four PET tracers for brain hypoxia mapping in a rodent model of stroke

IntroductionSevere 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 18F-fluoromisonidazole (18F-FMISO). However, the utility of 18F-FMISO is limited by its slow accumulation in the lesion. Therefore, this study investigated three hypoxia-sensitive radiotracers, namely the nitroimidazole 18F-fluoroazomycin arabinoside (18F-FAZA) and two 64Cu bis(thiosemicarbazone) complexes (64Cu-ATSM and 64Cu-ATSE), expected to have improved pharmacokinetic profiles relative to 18F-FMISO, in a rodent model of ischemic stroke.MethodsIn anaesthetised Wistar rats, the distal middle cerebral artery was permanently occluded by electrocoagulation, the radiotracers administered intravenously and animals PET scanned for up to 3 hours, followed by T2-weighted magnetic resonance imaging to map the infarct.ResultsAs expected, late and prominent 18F-FMISO retention was observed despite lower tracer delivery into the affected region. Time-activity curves revealed that both 64Cu-ATSM and 64Cu-ATSE showed rapid entry and efflux from the brain, but did not show significant accumulation in the lesion. 18F-FAZA showed limited brain penetration, and accumulation in the lesion was inconsistent, low and as slow as 18F-FMISO.ConclusionsThis study suggests further development of these radiotracers as hypoxia markers for ischemic stroke may not be warranted.