title: Kinetic modelling of [11C]flumazenil using data-driven methods.
abstract: OBJECTIVE
  [(11)C]Flumazenil (FMZ) is a benzodiazepine receptor antagonist that binds reversibly to central-type gamma-aminobutyric acid (GABA-A) sites. A validated approach for analysis of [(11)C]FMZ is the invasive one-tissue (1T) compartmental model. However, it would be advantageous to analyse FMZ binding with whole-brain pixel-based methods that do not require a-priori hypotheses regarding preselected regions. Therefore, in this study we compared invasive and noninvasive data-driven methods (Logan graphical analysis, LGA; multilinear reference tissue model, MRTM2; spectral analysis, SA; basis pursuit denoising, BPD) with the 1T model.
  
  
  METHODS
  We focused on two aspects: (1) replacing the arterial input function analyses with a reference tissue method using the pons as the reference tissue, and (2) shortening the scan protocol from 90 min to 60 min. Dynamic PET scans were conducted in seven healthy volunteers with arterial blood sampling. Distribution volume ratios (DVRs) were selected as the common outcome measure.
  
  
  RESULTS
  The SA, LGA with and without arterial input, and MRTM2 agreed best with the 1T model DVR values. The invasive and noninvasive BPD were slightly less well correlated. The full protocol of a 90-min emission data performed better than the 60-min protocol, but the 60-min protocol still delivered useful data, as assessed by the coefficient of variation, and the correlation and bias analyses.
  
  
  CONCLUSIONS
  This study showed that the SA, LGA and MRTM2 are valid methods for the quantification of benzodiazepine receptor binding with [(11)C]FMZ using an invasive or noninvasive protocol, and therefore have the potential to reduce the invasiveness of the procedure.
authors.affiliation: Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. isabelle.miederer@tum.de
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miederer
authors.forename: Sibylle I
authors.initials: SI
authors.lastname: Ziegler
authors.forename: Christoph
authors.initials: C
authors.lastname: Liedtke
authors.forename: Mary E
authors.initials: ME
authors.lastname: Spilker
authors.forename: Matthias
authors.initials: M
authors.lastname: Miederer
authors.forename: Till
authors.initials: T
authors.lastname: Sprenger
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Wagner
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.forename: Henning
authors.initials: H
authors.lastname: Boecker
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D005260:Female; D005442:Flumazenil / Q000737:chemistry* / Q000494:pharmacology*; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000737:chemistry; D013997:Time Factors
chemical_list: D018757:GABA Modulators; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A; D019788:Fluorodeoxyglucose F18; D005442:Flumazenil