title: Quantitative analyses of 18F-FEDAA1106 binding to peripheral benzodiazepine receptors in living human brain.
abstract: N-(5-Fluoro-2-phenoxyphenyl)-N-(2-(18)F-fluoroethyl-5-methoxybenzyl)acetamide ((18)F-FEDAA1106) is a potential PET ligand with highly selective and specific binding to peripheral benzodiazepine receptor (PBR). It has been reported that the regional density of PBR in the brain is increased in several neurodegenerative and psychiatric disorders. Thus, a reliable tracer method for evaluating PBR would be of use clinically and for research. To our knowledge, this is the first study to investigate the (18)F-FEDAA1106 binding to PBR in living human brain by PET. We also aimed to evaluate various analytic methods to quantify the density of PBR.
  
  
  METHODS
  PET studies with (18)F-FEDAA1106 were performed on 7 healthy men. Volumes of interest (VOIs) were drawn on PET images. In each VOI, binding potential (BP) was calculated by nonlinear least-squares (NLS) fitting based on the 2-tissue compartment model, and the distribution volume (DV) was also estimated by NLS, Logan plot, and multilinear analysis (MA) methods. To estimate errors in calculation of BP and DV, simulation studies were also performed.
  
  
  RESULTS
  The DVs estimated with each of the methods were significantly correlated. There was also significant correlation between BP with NLS and DV with NLS, Logan plot, or MA. But the interindividual differences in the distribution volume of the free and nonspecific binding compartment (K(1)/k(2)) were relatively large. In a simulation study, variation of the DV estimated by Logan plot was relatively small, but it was underestimated as the noise increased. By MA, the bias of DV was smaller, but the variation of DV was larger than by Logan plot. Within a 3% noise level, there was almost no difference between Logan plot and MA in both bias and variation. DVs estimated by both Logan plot and MA were underestimated by 10%-20%. Although the variation of DV was larger by NLS than by Logan plot, it was small enough in the noise level of VOI analysis, and the bias of DV was 0%-2%.
  
  
  CONCLUSIONS
  The simulation studies indicated that NLS is a suitable method for the estimation of (18)F-FEDAA1106 binding to PBRs.
authors.affiliation: Brain Imaging Project, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Yota
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikoma
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yasuno
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.forename: Miho
authors.initials: M
authors.lastname: Ota
authors.forename: Ryohei
authors.initials: R
authors.lastname: Matsumoto
authors.forename: Shoko
authors.initials: S
authors.lastname: Nozaki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takano
authors.forename: Jun
authors.initials: J
authors.lastname: Kosaka
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Ryuji
authors.initials: R
authors.lastname: Nakao
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
mesh_terms: D000081:Acetamides / Q000493:pharmacokinetics*; D000328:Adult; D001665:Binding Sites; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D011485:Protein Binding; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D000081:Acetamides; C475621:N-(5-fluoro-2-phenoxyphenyl)-N-(2-fluoroethyl-5-methoxybenzyl)acetamide; D019275:Radiopharmaceuticals; D011963:Receptors, GABA-A