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J Nucl Med. 2008; 49 (Supplement 1):81P
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Neurosciences: Basic Science

Imaging Markers of Neuropathology

PET imaging of VEGF receptor expression after experimental focal stroke

Weibo Cai1, Raphael Guzman1, Andrew Hsu1, Guohua Sun1, Hui Wang1, Michael Mosley1, Heng Zhao1, Gary Steinberg1 and Xiaoyuan Chen1

1 Stanford University, Stanford, California


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Objectives: To date, no treatment exists to restore the lost neurological function after stroke. As new therapies (e.g. cell transplantation) for stroke emerge, molecular imaging will be an invaluable tool for optimizing and monitoring such intervention. Herein, we evaluated the kinetics of vascular endothelial growth factor receptor (VEGFR) expression during post-stroke angiogenesis in a rat model.

Methods: In female Sprague-Dawley rats, stroke was created by permanent distal middle cerebral artery occlusion (dMCAo). The rats were subjected to weekly MRI, 18F-FDG PET, and 64Cu-DOTA-VEGF121 PET scans after surgery. Several control experiments (sham-operated rats; the use of a VEGFmutant which does not bind to VEGFR-2 based on competitive cell binding assay) were performed to confirm the VEGFR specificity of 64Cu-DOTA-VEGF121 uptake in the penumbra. Histology and autoradiography was carried out to validate the imaging results.

Results: Stroke in the rat brain was confirmed by T2-weighed MRI and a "cold spot" in 18F-FDG PET. 64Cu-DOTA-VEGF121 uptake in the penumbra peaked at 10 days after surgery, indicating angiogenesis as confirmed by histology (strong VEGFR and BrdU staining in the penumbra, both co-localizing with the vasculature). VEGFR specificity of 64Cu-DOTA-VEGF121 uptake was confirmed by low uptake of 64Cu-DOTA-VEGFmutant in the penumbra, minimal 64Cu-DOTA-VEGF121 uptake in the brain of sham-operated rats, and 125I-VEGF165 autoradiography of the brain tissue.

Conclusions: We successfully evaluated the VEGFR expression kinetics non-invasively in an experimental stroke model. PET imaging of VEGFR expression, thereby non-invasively evaluating angiogenesis, may be translated into the clinic to determine the right timing and to monitor the therapeutic efficacy of new therapies (such as stem cell transplantation) for stroke.





This Article
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Right arrow Articles by Chen, X.
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Right arrow Articles by Cai, W.
Right arrow Articles by Chen, X.