on October 23, 2008
Published online before print October 23, 2008, doi: 10.1161/STROKEAHA.108.517474
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Submitted on February 14, 2008
From The Molecular Imaging Program at Stanford (W.C., A.R.H, H.W., L.H., K.C., Z-B.L., M.M., X.C.), Department of Radiology, Stanford University, Calif; Departments of Radiology and Medical Physics (W.C.), University of Wisconsin–Madison, Wis; Department of Neurosurgery (R.G., G.S., A.G., R.C., T.B., A-L.D.M., N.H., H.Z., G.K.S.), Stanford University, Calif. * To whom correspondence should be addressed. E-mail: shawchen{at}stanford.edu.
Background and Purpose—Vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFRs) play important roles during neurovascular repair after stroke. In this study, we imaged VEGFR expression with positron emission tomography (PET) to noninvasively analyze poststroke angiogenesis. Methods—Female Sprague-Dawley rats after distal middle cerebral artery occlusion surgery were subjected to weekly MRI, 18F-FDG PET, and 64Cu-DOTA-VEGF121 PET scans. Several control experiments were performed to confirm the VEGFR specificity of 64Cu-DOTA-VEGF121 uptake in the stroke border zone. VEGFR, BrdU, lectin staining, and 125I-VEGF165 autoradiography on stroke brain tissue slices were performed to validate the in vivo findings. Results—T2-weighed MRI correlated with the "cold spot" on 18F-FDG PET for rats undergoing distal middle cerebral artery occlusion surgery. The 64Cu-DOTA-VEGF121 uptake in the stroke border zone peaked at Conclusions—For the first time to our knowledge, we successfully evaluated the VEGFR expression kinetics noninvasively in a rat stroke model. In vivo imaging of VEGFR expression could become a significant clinical tool to plan and monitor therapies aimed at improving poststroke angiogenesis.
Revised on April 24, 2008
Accepted on May 29, 2008
Positron Emission Tomography Imaging of Poststroke Angiogenesis
Weibo Cai PhD;
10 days after surgery, indicating neovascularization as confirmed by histology (VEGFR-2, BrdU, and lectin staining). VEGFR specificity of 64Cu-DOTA-VEGF121 uptake was confirmed by significantly lower uptake of 64Cu-DOTA-VEGFmutant in vivo and intense 125I-VEGF165 uptake ex vivo in the stroke border zone. No appreciable uptake of 64Cu-DOTA-VEGF121 was observed in the brain of sham-operated rats.
Key words: positron emission tomography • stroke • vascular endothelial growth factor receptor