PET Imaging of Stroke-Induced Neuroinflammation in Mice Using [18F]PBR06
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The purpose of this study is to evaluate the 18 kDa translocator protein (TSPO) radioligand [18F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([18F]PBR06) as a positron emission tomography (PET) imaging biomarker of stroke-induced neuroinflammation in a rodent model.
Stroke was induced by transient middle cerebral artery occlusion in Balb/c mice. Dynamic PET/CT imaging with displacement and preblocking using PK111195 was performed 3 days later. PET data were correlated with immunohistochemistry (IHC) for the activated microglial markers TSPO and CD68 and with autoradiography.
[18F]PBR06 accumulation peaked within the first 5 min postinjection, then decreased gradually, remaining significantly higher in infarct compared to noninfarct regions. Displacement or preblocking with PK11195 eliminated the difference in [18F]PBR06 uptake between infarct and noninfarct regions. Autoradiography and IHC correlated well spatially with uptake on PET.
[18F]PBR06 PET specifically images TSPO in microglial neuroinflammation in a mouse model of stroke and shows promise for imaging and monitoring microglial activation/neuroinflammation in other disease models.
Key wordsStroke Neuroinflammation Translocator protein 18 kDa (TSPO) Peripheral benzodiazepine receptor (PBR) Positron emission tomography (PET) [18F]PBR06
The authors thank Dr. Victor W. Pike and the National Institute of Mental Health for providing the [18F]PBR06 precursor and standard, Dr. Makoto Higuchi of the National Institute of Radiological Sciences, Japan, for providing the TSPO antibody and the Stanford Center for Innovation in In Vivo Imaging. The study was supported in part by a Bio-X Interdisciplinary Initiatives Program (IIP) award from Stanford University (to BWL), a Developmental Cancer Research Award (DCRA) in Translational Research from Stanford Cancer Institute (to BWL), a NCI ICMIC P50 award (CA114747 to Dr. Sanjiv Sam Gambhir), an American Heart Association Grant (AHA-0835274 N to RG), a CIRM grant (RC1-0134 to TDP), grants from the National Research Foundation of Korea and the Ministry of Education, Science and Technology, Korea (R31-10105 and NRF-2012M3A9C6049796 to G-OA), and the Department of Radiation Oncology, Stanford University.
Conflict of Interest
The authors declare that they have no conflicts of interest relevant to this study.
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