title: Kinetic analysis of the translocator protein positron emission tomography ligand [18F]GE-180 in the human brain.
abstract: OBJECTIVE
  PET can image neuroinflammation by targeting the translocator protein (TSPO), which is upregulated in activated microglia. The high nonspecific binding of the first-generation TSPO radioligand [11C]PK-11195 limits accurate quantification. [18F]GE-180, a novel TSPO ligand, displays superior binding to [11C]PK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of [18F]GE-180 in the brains of healthy human subjects; and (2) investigate whether the TSPO Ala147Thr polymorphism influences outcome measures.
  
  
  METHODS
  Ten volunteers (five high-affinity binders, HABs, and five mixed-affinity binders, MABs) underwent a dynamic PET scan with arterial sampling after injection of [18F]GE-180. Kinetic modelling of time-activity curves with one-tissue and two-tissue compartment models and Logan graphical analysis was applied to the data. The primary outcome measure was the total volume of distribution (VT) across various regions of interest (ROIs). Secondary outcome measures were the standardized uptake values (SUV), the distribution volume and SUV ratios estimated using a pseudoreference region.
  
  
  RESULTS
  The two-tissue compartment model was the best model. The average regional delivery rate constant (K1) was 0.01 mL cm-3min-1indicating low extraction across the blood-brain barrier (1 %). The estimated median VTacross all ROIs was also low, ranging from 0.16 mL cm-3in the striatum to 0.38 mL cm-3in the thalamus. There were no significant differences in VTbetween HABs and MABs across all ROIs.
  
  
  CONCLUSIONS
  A reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction (approximately 1 %) and low VTestimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of [18F]GE-180 in populations with neuroinflammatory disease is needed to determine its suitability for quantitative assessment of TSPO expression.
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK. c.feeney@imperial.ac.uk.|Computational, Cognitive and Clinical Neuroimaging Laboratory, Hammersmith Hospital, 3rd Floor, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK. c.feeney@imperial.ac.uk.
authors.forename: Claire
authors.initials: C
authors.lastname: Feeney
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK.
authors.forename: Gregory
authors.initials: G
authors.lastname: Scott
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK.
authors.forename: Joel
authors.initials: J
authors.lastname: Raffel
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Roberts
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Coello
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK.
authors.forename: Amy
authors.initials: A
authors.lastname: Jolly
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Searle
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Goldstone
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK.|Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Nicholas
authors.affiliation: GE Healthcare Ltd, Amersham, UK.
authors.forename: William
authors.initials: W
authors.lastname: Trigg
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK.
authors.forename: Roger N
authors.initials: RN
authors.lastname: Gunn
authors.affiliation: Division of Brain Sciences, Hammersmith Hospital Campus, Imperial College London, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Sharp
mesh_terms: D000328:Adult; D000465:Algorithms; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002227:Carbazoles / Q000493:pharmacokinetics*; D003198:Computer Simulation; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007700:Kinetics; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008959:Models, Neurological; D057054:Molecular Imaging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D018079:Receptors, GABA / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D002227:Carbazoles; C571664:GE-180; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human
keywords: GE180; Kinetic analysis; Neuroinflammation; Positron emission tomography (PET); Quantification; Translocator protein (TSPO)