Background: P-selectin is activated early after stroke, followed by a rapid decline. This
time course can be used to generate important information on stroke onset. The latter is crucial for
therapeutic decision-making of wake-up strokes (i.e. thrombolysis or not). Here, we evaluated the
specific p-selectin inhibitor fucoidan labeled with gallium-68 (68Ga-Fucoidan) as an imaging biomarker
for assessing p-selectin activation in acute ischemic stroke using Positron Emission Tomography
Methods: 68Ga-Fucoidan was investigated in rats brain at 2-5 h (n=16), and additionally at 24-26 h
(n=9) and 48 h (n=3) after induction of photothrombic stroke or in sham-operated animals (n=6).
Correlation of cerebral 68Ga-Fucoidan uptake with p-selectin expression was determined by exposing
freshly cut brain cryosections to autoradiography and immunostaining using specific antibodies
Results: PET scans showed an increased accumulation of 68Ga-Fucoidan in the histologically
proven ischemic stroke, as compared to the corresponding contralateral hemisphere in all except
one animal. The median ratio between the uptake in the ischemic lesion and the contralateral region
was 1.95 (1.45-2.41) at 2-5 h, 1.38 (1.05-1.89) at 24-26 h, and 1.09 (0.81-1.38) at 48 h after
stroke, compared to 1.22 (0.99-1.49) for sham-operated animals. In the ex vivo autoradiography,
68Ga-Fucoidan accumulation co-localized with p-selectin as assessed by immunostaining. Control
animals and those scanned at 24-26 h and 48 h after stroke exhibited no elevated 68Ga-Fucoidan
uptake in either hemisphere.
Conclusion: PET imaging using 68Ga-Fucoidan represents a valuable tool for assessing p-selectin
activation in vivo discriminating ischemic stroke early after stroke onset.