title: PET imaging of translocator protein (18 kDa) in a mouse model of Alzheimer's disease using N-(2,5-dimethoxybenzyl)-2-18F-fluoro-N-(2-phenoxyphenyl)acetamide.
abstract: Herein we aimed to evaluate the utility of N-(2,5-dimethoxybenzyl)-2-(18)F-fluoro-N-(2-phenoxyphenyl)acetamide ((18)F-PBR06) for detecting alterations in translocator protein (TSPO) (18 kDa), a biomarker of microglial activation, in a mouse model of Alzheimer's disease (AD).
  
  
  METHODS
  Wild-type (wt) and AD mice (i.e., APP(L/S)) underwent (18)F-PBR06 PET imaging at predetermined time points between the ages of 5-6 and 15-16 mo. MR images were fused with PET/CT data to quantify (18)F-PBR06 uptake in the hippocampus and cortex. Ex vivo autoradiography and TSPO/CD68 immunostaining were also performed using brain tissue from these mice.
  
  
  RESULTS
  PET images showed significantly higher accumulation of (18)F-PBR06 in the cortex and hippocampus of 15- to 16-mo-old APP(L/S) mice than age-matched wts (cortex/muscle: 2.43 ± 0.19 vs. 1.55 ± 0.15, P < 0.005; hippocampus/muscle: 2.41 ± 0.13 vs. 1.55 ± 0.12, P < 0.005). And although no significant difference was found between wt and APP(L/S) mice aged 9-10 mo or less using PET (P = 0.64), we were able to visualize and quantify a significant difference in (18)F-PBR06 uptake in these mice using autoradiography (cortex/striatum: 1.13 ± 0.04 vs. 0.96 ± 0.01, P < 0.05; hippocampus/striatum: 1.266 ± 0.003 vs. 1.096 ± 0.017, P < 0.001). PET results for 15- to 16-mo-old mice correlated well with autoradiography and immunostaining (i.e., increased (18)F-PBR06 uptake in brain regions containing elevated CD68 and TSPO staining in APP(L/S) mice, compared with wts).
  
  
  CONCLUSIONS
  (18)F-PBR06 shows great potential as a tool for visualizing TSPO/microglia in the progression and treatment of AD.
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California Department of Neurology and Neurological Sciences, Stanford University, Stanford, California; and.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: James
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, California; and.
authors.forename: Nadia P
authors.initials: NP
authors.lastname: Belichenko
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, California; and.
authors.forename: Thuy-Vi V
authors.initials: TV
authors.lastname: Nguyen
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Andrews
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, California; and Veterans Administration Palo Alto Health Care System, Palo Alto, California.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California.
authors.forename: Deepika
authors.initials: D
authors.lastname: Bodapati
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California.
authors.forename: Natasha
authors.initials: N
authors.lastname: Arksey
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California.
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, California; and Veterans Administration Palo Alto Health Care System, Palo Alto, California.
authors.forename: Tony
authors.initials: T
authors.lastname: Wyss-Coray
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California.
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, California; and.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Longo
authors.affiliation: Department of Radiology, Molecular Imaging Program at Stanford (MIPS), Stanford University, Stanford, California chinf@stanford.edu.
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Chin
mesh_terms: D000083:Acetanilides; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001345:Autoradiography; D015415:Biomarkers / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D051379:Mice; D009132:Muscles / Q000378:metabolism; D049268:Positron-Emission Tomography; D018079:Receptors, GABA / Q000378:metabolism*; D015203:Reproducibility of Results; D013997:Time Factors; D000097382:CD68 Molecule
chemical_list: D000083:Acetanilides; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D018079:Receptors, GABA; C463819:Bzrp protein, mouse; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C538798:N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline
keywords: Alzheimer's disease; PET; microglial activation; translocator protein 18 kDa