Imaging the ischemic penumbra with 18F-fluoromisonidazole in a rat model of ischemic stroke.
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.
Saita
Kazuko
K
Department of Medicine, University of Melbourne, Austin Health, Melbourne, Victoria, Australia.
Chen
Michelle
M
Spratt
Neil J
NJ
Porritt
Michelle J
MJ
Liberatore
Gabriel T
GT
Read
Stephen J
SJ
Levi
Christopher R
CR
Donnan
Geoffrey A
GA
Ackermann
Uwe
U
Tochon-Danguy
Henri J
HJ
Sachinidis
John I
JI
Howells
David W
DW
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
C031843:fluoromisonidazole; D008920:Misonidazole