title: In vivo imaging of the 18-kDa translocator protein (TSPO) with [18F]FEDAA1106 and PET does not show increased binding in Alzheimer's disease patients.
abstract: OBJECTIVE
  Imaging the 18-kDa translocator protein (TSPO) is considered a potential tool for in vivo evaluation of microglial activation and neuroinflammation in the early stages of Alzheimer's disease (AD). ((R)-1-(2-chlorophenyl)-N-[(11)C]-methyl-N-(1-methylpropyl)-3-isoquinoline caboxamide ([(11)C]-(R)-PK11195) has been widely used for PET imaging of TSPO and, despite its low specific-to-nondisplaceable binding ratio, increased TSPO binding has been shown in AD patients. The high-affinity radioligand N-(5-fluoro-2-phenoxyphenyl)-N-(2-[(18)F]fluoroethyl-5-methoxybenzyl)acetamide ([(18)F]FEDAA1106) has been developed as a potential in vivo imaging tool for better quantification of TSPO binding. The aim of this study was to quantify in vivo binding of [(18)F]FEDAA1106 to TSPO in control subjects and AD patients.
  
  
  METHODS
  Seven controls (five men, two women, age 68±3 years, MMSE score 29±1) and nine AD patients (six men, three women, age 69±4 years, MMSE score 25±3) were studied with [(18)F]FEDAA1106. PET measurements were performed on an ECAT EXACT HR system (Siemens Medical Solutions) in two 60-min dynamic PET sessions with a 30-min interval between sessions. Arterial blood radioactivity was measured using an automated blood sampling system for the first 5 min and using manually drawn samples thereafter. Quantification was performed using both kinetic analysis based on a two-tissue compartment model and Logan graphical analysis. Outcome measures were total distribution volume (V T) and binding potential (BP(ND)=k3/k4). An estimate of nondisplaceable distribution volume was obtained with the Logan graphical analysis using the first 15 min of PET measurements (V(ND 1-15 min)). Binding potential (BP(ND)) was also calculated as: V(T)/V(ND 1-15 min) - 1.
  
  
  RESULTS
  No statistically significant differences in V(T), k3/k4 or BP(ND) were observed between controls and AD patients.
  
  
  CONCLUSIONS
  This study suggests that TSPO imaging with [(18)F]FEDAA1106 does not enable the detection of microglial activation in AD.
authors: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Hospital, Stockholm, Sweden. andrea.varrone@ki.se
authors: Andrea
authors: A
authors: Varrone
authors: Patrik
authors: P
authors: Mattsson
authors: Anton
authors: A
authors: Forsberg
authors: Akihiro
authors: A
authors: Takano
authors: Sangram
authors: S
authors: Nag
authors: Balázs
authors: B
authors: Gulyás
authors: Jacqueline
authors: J
authors: Borg
authors: Ronald
authors: R
authors: Boellaard
authors: Nabil
authors: N
authors: Al-Tawil
authors: Maria
authors: M
authors: Eriksdotter
authors: Torsten
authors: T
authors: Zimmermann
authors: Marcus
authors: M
authors: Schultze-Mosgau
authors: Andrea
authors: A
authors: Thiele
authors: Anja
authors: A
authors: Hoffmann
authors: Adriaan A
authors: AA
authors: Lammertsma
authors: Christer
authors: C
authors: Halldin
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology*; D001331:Automation; D001931:Brain Mapping; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D018079:Receptors, GABA / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; C475621:N-(5-fluoro-2-phenoxyphenyl)-N-(2-fluoroethyl-5-methoxybenzyl)acetamide; D018079:Receptors, GABA; C499229:TSPO protein, human; D019788:Fluorodeoxyglucose F18