PET Imaging of Stroke-Induced Neuroinflammation in Mice Using [F-18]PBR06

• Type of Material: Article
• Authors: Frederick M. Lartey, Stanford University; G-One Ahn, Stanford University; Bin Shen, Stanford University; Keith-Travis Cord, Stanford University; Tenille Smith, Stanford University; Joshua Y. Chua, Stanford University; Sahar Rosenblum, Stanford University; Hongguang Liu, Stanford University; Michelle L. James, Stanford University; Sophia Chernikova, Stanford University; Star W. Lee, Stanford University; Laura J. Pisani, Stanford University; Rabindra Tirouvanziam, Emory University; John W. Chen, Harvard University; Theo D. Palmer, Stanford University; Frederick T. Chin, Stanford University; Raphael Guzman, Stanford University; Edward E. Graves, Stanford University; Billy W. Jr. Loo, Stanford University
• Language: English
• Date: 2014-02-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 World Molecular Imaging Society.
• Final Published Version (URL): http://dx.doi.org/10.1007/s11307-013-0664-5
• Title of Journal or Parent Work: Molecular Imaging and Biology
• ISSN: 1536-1632
• Volume: 16
• Issue: 1
• Start Page: 109
• End Page: 117
• Grant/Funding Information: 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.
• Keywords: Translocator protein 18 kDa (TSPO); Stroke; INFLAMMATORY RESPONSE; Neuroinflammation; PERMANENT; Positron emission tomography (PET); PROTEIN 18 KDA; PERIPHERAL BENZODIAZEPINE-RECEPTORS; MICROGLIA; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-ISCHEMIA; Peripheral benzodiazepine receptor (PBR); Life Sciences & Biomedicine; Radiology, Nuclear Medicine & Medical Imaging; BRAIN; IN-VIVO; LIGAND; [F-18]PBR06; Science & Technology
• Research Categories: Biology, Neuroscience; Biology, Animal Physiology; Biophysics, Medical

Abstract

Purpose: 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. Procedures: 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. Results: [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. Conclusions: [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.