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@ARTICLE{Sabri:131879,
      author       = {Sabri, O and Wilke, S and Gräf, S and Lengler, U and
                      Gertz, H and Schönknecht, P and Habermann, B and Becker, G
                      and Luthardt, J and Patt, M and Kendziorra, K and Meyer, P
                      and Hesse, S and Barthel, H and Steinbach, J and
                      Wagenknecht, Gudrun and Höpping, A and Hegerl, U and Brust,
                      P},
      title        = {{F}irst in man study with the new radioligand
                      {F}-18-{F}lubatine to image alpha4beta2 cerebral nicotinic
                      acetylcholine receptors (n{AC}h{R}s) in early
                      {A}lzheimer’s disease ({AD}) with {PET}},
      journal      = {Nuklearmedizin},
      volume       = {51},
      number       = {2},
      issn         = {0029-5566},
      address      = {Stuttgart},
      publisher    = {Schattauer},
      reportid     = {FZJ-2013-01139},
      pages        = {A33},
      year         = {2012},
      abstract     = {Ziel/Aim: Using F-18-A85380 (2FA) PET we recently
                      demonstrated significant cerebral nAChR declines in early AD
                      which correlated significantly with the loss of cognitive
                      function (1-2). However, 2FA is not well suited in clinical
                      routine use because of slow kinetics, acquisition times up
                      to 7 hours, and limited nAChR selectivity. Thus, we
                      developed the new tracer F-18-Flubatine, an epibatidine
                      derivative without toxicity in humans formerly named as
                      F-18-NCFHEB (3) and report here on the worldwide first human
                      Flubatine-PET results. Methodik/Methods: 16 mild AD patients
                      (NINCDS-ADRDA, age 74.4±6.6, MMSE 23.7±2.8) and 11
                      age-matched healthy controls (HCs, MMSE 28.5±0.9), all
                      nonsmokers and nave for central acting medication, underwent
                      Flubatine- PET (370 MBq, 3D-acquisition, ECAT Exact HR+).
                      Dynamic 0-270min p.i. scans were acquired and corrected for
                      motion (SPM2). Kinetic modeling was applied to 29 brain
                      VOI-based tissue-activity curves (VOIs defined on individual
                      MRI) using a one-tissue compartment model with measured
                      arterial input function. Total distribution volume (DV) and
                      binding potential (BP, reference region: corpus callosum)
                      were used to characterize specific binding.
                      Ergebnisse/Results: Image quality of Flubatine scans was
                      clearly superior to 2FA, and a 20 minutes scan already
                      adequate for visual analysis. All 29 regions were well
                      described with one-tissue compartment. PET data acquired
                      over only 90 minutes were sufficient to estimate all kinetic
                      parameters precisely indicating a fast receptor binding
                      kinetic (much faster than for 2FA). DVs in HCs increase as
                      expected with receptor density: Corpus callosum (DV:
                      4.81±0.32), posterior cingulate (8.92±0.66), temporal
                      (9.03±0.44), pons (11.00±1.19), thalamus (24.32±2.96).
                      The AD patients showed extensive BP reductions in frontal,
                      parietal, temporal, anterior and posterior cingulate
                      cortices, caudate, and midbrain (all p<0.05) compared to
                      HCs. There was significant correlation between nAChR
                      reductions and cognitive declines in posterior cingulate,
                      parietal, and temporal cortices, as well as in pons and
                      cerebellum (p<0.05, all r> 0.41).
                      Schlussfolgerungen/Conclusions: Due to the significant
                      shorter acquisition time and superior image quality
                      Flubatine appears to be a much more valuable tracer than 2FA
                      to image nAChRs in humans. Early AD patients show
                      significant declines of nAChRs in brain regions typically
                      affected by AD pathology which correlate well with the
                      corresponding cognitive declines. These results indicate
                      that Flubatine-PET has a great potential as a biomarker for
                      early AD diagnosis. Literatur/References: (1) Sabri et al.
                      Eur J Nucl Med Mol Imaging 2008; 35 (Suppl. 1): 30-45 (2)
                      Kendziorra et al., Eur J Nucl Med Mol Imaging 2011; 38:
                      515-525 (3) Brust et al. Synapse 2008; 62: 205-218 This
                      trial is granted by the German Federal Ministry of Education
                      and Research (BMBF-Nr. 01EZ0820)},
      month         = {Apr},
      date          = {2012-04-25},
      organization  = {50. Jahrestagung der Deutschen
                       Gesellschaft für Nuklearmedizin,
                       Bremen (Germany), 25 Apr 2012 - 28 Apr
                       2012},
      cin          = {ZEL / ZEA-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)ZEL-20090406 / I:(DE-Juel1)ZEA-2-20090406},
      pnm          = {333 - Pathophysiological Mechanisms of Neurological and
                      Psychiatric Diseases (POF2-333) / BMBF-01EZ0822 -
                      NorChloro-Fluoro HomoEpiBatidin (NCFHEB) ein potentieller
                      Positronen-Emission Tomographie-(PET) Marker der frühen
                      Alzheimer-Demenz (BMBF-01EZ0822)},
      pid          = {G:(DE-HGF)POF2-333 / G:(DE-Juel1)BMBF-01EZ0822},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:22434155},
      UT           = {WOS:000303267400002},
      doi          = {10.3413/Nukmed-2012020001},
      url          = {https://juser.fz-juelich.de/record/131879},
}