title: Glial Activation and Glucose Metabolism in a Transgenic Amyloid Mouse Model: A Triple-Tracer PET Study.
abstract: Amyloid imaging by small-animal PET in models of Alzheimer disease (AD) offers the possibility to track amyloidogenesis and brain energy metabolism. Because microglial activation is thought to contribute to AD pathology, we undertook a triple-tracer small-animal PET study to assess microglial activation and glucose metabolism in association with amyloid plaque load in a transgenic AD mouse model.
  
  
  
  Groups of PS2APP and C57BL/6 wild-type mice of various ages were examined by small-animal PET. We acquired 90-min dynamic emission data with (18)F-GE180 for imaging activated microglia (18-kD translocator protein ligand [TSPO]) and static 30- to 60-min recordings with (18)F-FDG for energy metabolism and (18)F-florbetaben for amyloidosis. Optimal fusion of PET data was obtained through automatic nonlinear spatial normalization, and SUVRs were calculated. For the novel TSPO tracer (18)F-GE180, we then calculated distribution volume ratios after establishing a suitable reference region. Immunohistochemical analyses with TSPO antisera, methoxy-X04 staining for fibrillary β-amyloid, and ex vivo autoradiography served as terminal gold standard assessments.
  
  
  
  SUVR at 60-90 min after injection gave robust quantitation of (18)F-GE180, which correlated well with distribution volume ratios calculated from the entire recording and using a white matter reference region. Relative to age-matched wild-type, (18)F-GE180 SUVR was slightly elevated in PS2APP mice at 5 mo (+9%; P < 0.01) and distinctly increased at 16 mo (+25%; P < 0.001). Over this age range, there was a high positive correlation between small-animal PET findings of microglial activation with amyloid load (R = 0.85; P < 0.001) and likewise with metabolism (R = 0.61; P < 0.005). Immunohistochemical and autoradiographic findings confirmed the in vivo small-animal PET data.
  
  
  
  In this first triple-tracer small-animal PET in a well-established AD mouse model, we found evidence for age-dependent microglial activation. This activation, correlating positively with the amyloid load, implies a relationship between amyloidosis and inflammation in the PS2APP AD mouse model.
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Brendel
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Federico
authors.initials: F
authors.lastname: Probst
authors.affiliation: DZNE-German Center for Neurodegenerative Diseases, Munich, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Jaworska
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Overhoff
authors.affiliation: DZNE-German Center for Neurodegenerative Diseases, Munich, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Korzhova
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Nathalie L
authors.initials: NL
authors.lastname: Albert
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Beck
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Lindner
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Gildehaus
authors.affiliation: Roche Pharma Research and Early Development, Neuroscience Discovery, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Baumann
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany SyNergy, Ludwig-Maximilians-University of Munich, Munich, Germany; and.
authors.forename: Peter
authors.initials: P
authors.lastname: Bartenstein
authors.affiliation: DZNE-German Center for Neurodegenerative Diseases, Munich, Germany SyNergy, Ludwig-Maximilians-University of Munich, Munich, Germany; and Biomedical Center (BMC), Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Kleinberger
authors.affiliation: DZNE-German Center for Neurodegenerative Diseases, Munich, Germany SyNergy, Ludwig-Maximilians-University of Munich, Munich, Germany; and Biomedical Center (BMC), Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Haass
authors.affiliation: DZNE-German Center for Neurodegenerative Diseases, Munich, Germany SyNergy, Ludwig-Maximilians-University of Munich, Munich, Germany; and.
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
authors.affiliation: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany SyNergy, Ludwig-Maximilians-University of Munich, Munich, Germany; and axel.rominger@med.uni-muenchen.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Rominger
mesh_terms: D000686:Amyloidosis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002227:Carbazoles; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000473:pathology*; D049268:Positron-Emission Tomography / Q000379:methods* / Q000592:standards; D011849:Radioactive Tracers; D012015:Reference Standards
chemical_list: D002227:Carbazoles; C571664:GE-180; D011849:Radioactive Tracers; D005947:Glucose
keywords: 18F-GE180; Alzheimer’s disease; TSPO; neuroinflammation; small animal PET