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@INPROCEEDINGS{Sabri:132105,
      author       = {Sabri, O (Corresponding author) and Wilke, S and Graef, S
                      and Lengler, U and Schoenknecht, P and Gertz, H and Becker,
                      G and Luthardt, J and Patt, M and Hesse, S and Barthel, H
                      and Wagenknecht, Gudrun and Hoepping, A and Hegerl, U and
                      Brust, P},
      title        = {{C}erebral {N}icotinic {A}cetylcholine {R}eceptors
                      (n{AC}h{R}s) {I}n {E}arly{A}lzheimer’s {D}isease ({AD})
                      {A}ssessed {W}ith {T}he {N}ew {R}adioligand
                      [18{F}]{F}lubatine and {PET}},
      reportid     = {FZJ-2013-01344},
      year         = {2012},
      abstract     = {Objectives: There is evidence from post‐mortem studies
                      that the loss of nAChRs, in particular of the
                      alpha4beta2‐nAChR, which is obviously most severely
                      reduced at the onset of AD, is a major contributor to the
                      cognitive deterioration in AD. Accordingly, using
                      2‐[18F]F‐A85380 PET we showed significant declines in
                      alpha4beta2‐nAChRs in early AD‐patients (Sabri et al.
                      2008; Kendziorra et al. 2010). However, this tracer was not
                      well suited as a biomarker in a routine clinical set‐up
                      for early AD‐diagnosis because of unfavourable properties
                      (especially long acquisition times up to 7 hours). We,
                      therefore, developed the new radiotracer (‐)‐
                      [18F]NCFHEB (denominated as [18F]Flubatine) with
                      significantly improved brain uptake and also better nAChR
                      affinity and selectivity (Brust et al. 2008). Here, we
                      present the results of the worldwide first ongoing
                      [18F]Flubatine‐PET study in humans. Methods: 19 mild
                      AD‐patients (NINCDS‐ADRDA, age 74.5±6.2, MMSE
                      23.7±2.7) and 20 age‐matched healthy controls (HC, age
                      70.6±4.6, MMSE 28.5±0.8) underwent [18F]Flubatine‐PET
                      (370 MBq, 3D‐acquisition, ECAT Exact HR+, 4 scans, 0‐270
                      min p.i., motion correction with SPM2). All were nonsmokers
                      and naïve for central acting medication. Kinetic modeling
                      was applied to the VOI‐based tissueactivity curves
                      generated for 29 brain regions. Total distribution volume
                      (DV) and binding potential (BP, reference region: corpus
                      callosum) were used to characterize specific binding.
                      Additionally, parametric images of DV were computed (Logan
                      plot). Results: Image quality of [18F]Flubatine scans was
                      clearly superior to 2‐[18F]FA85380, and a 20 minutes scan
                      already adequate for visual analysis. PET data acquired over
                      only 90 minutes were sufficient to estimate all kinetic
                      parameters of all VOIs with 1‐tissue compartment model.
                      Thirty‐minute scans were already sufficient for modelling
                      of all cortical VOIs. Tracer distribution was similar to
                      known alpha4beta2‐nAChR distribution and DVs in HCs
                      increase as expected with receptor density with the lowest
                      DV in the corpus callosum (5.64±0,87) and highest in the
                      thalamus (24.67±3.91). The AD‐patients showed significant
                      BP reductions in distinct cortical regions (p<0.05) compared
                      to HCs. Conclusions: Due to significant faster kinetics and
                      shorter acquisition time enabling full kinetic modeling
                      within 90 minutes, and superior image quality [18F]Flubatine
                      appears to be a much more suitable tracer than
                      2‐[18F]F‐A85380 to image alpha4beta2‐nAChRs in humans.
                      In keeping with its diagnostic properties, early
                      AD‐patients show declines of alpha4beta2‐nAChRs in
                      distinct cortical regions typically affected by
                      AD‐pathology. These results indicate that
                      [18F]Flubatine‐PET could have a great potential to be
                      tested as a biomarker for early AD‐diagnosis.},
      month         = {Oct},
      date          = {2012-10-27},
      organization  = {Annual Congress of the European
                       Association of Nuclear Medicine, Milan
                       (Italy), 27 Oct 2012 - 31 Oct 2012},
      subtyp        = {Other},
      cin          = {ZEL / ZEA-2},
      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)6},
      url          = {https://juser.fz-juelich.de/record/132105},
}