In
acute stroke, the target of
therapy is the severely hypoxic but salvageable tissue. Previous human studies using
18F-fluoromisonidazole and positron emission tomography (18F-FMISO PET) have shown high tracer retention indicative of tissue
hypoxia, which had normalized at repeat scan >48 h later. In the only validation study of
18F-FMISO, using ex vivo autoradiography in thread middle cerebral artery occluded (MCAo) rats, there was unexpected high uptake as late as 22 h after reperfusion, raising questions about the use of
18F-FMISO as a
hypoxia tracer. Here we report a pilot study of
18F-FMISO PET in experimental
stroke. Spontaneous hypertensive rats were subjected to distal
clip MCAo. Three-hour dynamic PET was performed in 7 rats: 3 normals, 1 with permanent MCAo (two sessions: 30 mins and 48 h after
clip), and 3 with temporary MCAo (45 mins, n=1; 120 mins, n=2; scanning started 30 mins after
clip removal). Experiments were terminated by perfusion-fixation for standard histopathology. Late tracer retention was assessed by both compartmental modelling and simple side-to-side ratios. In the initial PET session of the permanent MCAo rat, striking trapping of
18F-FMISO was observed in the affected cortex, which had normalized 48 h later; histopathology revealed pannecrosis. In contrast, there was no demonstrable tracer retention in either temporary MCAo models, and histopathology showed ischemic changes only. These results document elevated
18F-FMISO uptake in the
stroke area only in the early phase of MCAo, but not after early reperfusion nor when tissue
necrosis has developed. These findings strongly support the validity of
18F-FMISO as a marker of viable hypoxic tissue/penumbra after
stroke.